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At least 19 recordsLinked to original sources

PubMed2005

Cocaine addicts prone to cocaine-induced psychosis have lower body mass index than cocaine addicts resistant to cocaine-induced psychosis--Implications for the cocaine model of psychosis proneness.

BACKGROUND: The specific pathogenesis of increased vulnerability to cocaine-induced paranoia/psychosis is unknown. Weight loss has been long observed in patients abusing stimulants (including cocaine and the amphetamines). In the current study, we compared Body Mass Index (calculated as weight in kilograms divided by the square of height in meters) in Cocaine-Induced Psychosis cases, referred to as "Cocaine-Induced Psychosis-prone" (n=40) and non-Cocaine-Induced Psychosis cases, referred to as "Cocaine-Induced Psychosis-resistant" (n=29) consecutively admitted to a research substance abuse unit to determine whether Body Mass Index is associated with Cocaine-Induced Psychosis. Height and weight were measured and Body Mass Index calculated by a licensed nutritionist using a standardized protocol. Cocaine-induced psychosis and cocaine use patterns were assessed using the Cocaine Experience Questionnaire. RESULTS: Body Mass Index in the Cocaine-Induced Psychosis-prone patients was significantly lower than in the Cocaine-Induced Psychosis-resistant patients (i.e., 23.1 kg/m2 +/-2.5 vs. 25.4 kg/m2 +/-3.5 (P=.003), respectively). Percentage of Ideal Body Weight also differed significantly between the two groups. CONCLUSIONS: The data suggest that lower Body Mass Index may be associated with increasing proneness to developing psychotic symptoms in the context of crack cocaine use or that higher Body Mass Index might be associated with some protection against Cocaine-Induced Psychosis in the context of similar use patterns. In the Discussion the authors speculate as to why Cocaine-Induced Psychosis is more commonly observed in the patient population with lower Body Mass Index and lower percentage of Ideal Body Weight. They evoke possible involvement of cocaine's influence on the anorexigenic cytokine Tumor Necrosis Factor, Cocaine-and-Amphetamine-Regulated Transcript, or suppression of the appetite stimulating Neuropeptide Y, or cocaine-induced deficits in nicotinic cholinergic neural-transmission, all of which have not only been linked to weight and appetite, but also to idiopathic psychosis. It could be speculated that one or more of these systems might be differentially affected by cocaine addiction in the psychosis prone Cocaine-Induced Psychosis group vs. the psychosis resistant non-Cocaine-Induced Psychosis group. Further exploration of these possible associations seem warranted. Such findings would have implications for the cocaine model of psychosis proneness and perhaps for the stimulant model of psychoses in general.

Adult↗

PubMed1996

Systemic cocaine challenge after chronic cocaine treatment reveals sensitization of extracellular dopamine levels in nucleus accumbens but direct cocaine perfusion into nucleus accumbens does not: implications for the neural locus of cocaine sensitization.

Rats were treated chronically with 20 mg/kg/day cocaine (by intraperitoneal injection) for 16 days, followed by 7 days of cocaine wash-out. On the next day, rats were challenged with an acute dose of cocaine administered by one of two routes (systemic or intracranial), and extra-cellular dopamine (DA) in the nucleus accumbens (Acb) was measured by in vivo microdialysis. Rats acutely challenged systemically with 20 mg/kg cocaine showed enhanced Acb extracellular DA levels (compared to control rats that had not previously received chronic cocaine). However, rats acutely challenged with intracranial cocaine by perfusion of 10(-5) M cocaine directly into the Acb did not. It is suggested that both the development and triggering of cocaine sensitization, as manifested by enhanced Acb DA content to subsequent acute cocaine challenge, may involve more than just neural mechanisms occurring locally within the Acb.

Analysis of Variance↗

PubMedDate not supplied

Identification of cocaine in cocaine-lidocaine mixtures ("rock cocaine") and other illicit cocaine preparations using derivative absorption spectroscopy.

A rapid second-derivative procedure for distinguishing cocaine and other local anesthetics is described. This technique appeared to be particularly useful in the detection of cocaine in binary mixtures. It is of great value in forensic toxicology, resolving cocaine-lidocaine, cocaine-procaine, cocaine-tetracaine, and cocaine-benzocaine mixtures, for which zero-order UV spectroscopy fails.

Benzocaine↗

PubMed1999

Cocaine and alcohol interactions in the rat: effect of cocaine and alcohol pretreatments on cocaine pharmacokinetics and pharmacodynamics.

This experiment was designed to investigate the effect of pretreatment with cocaine and alcohol on cocaine pharmacokinetics and pharmacodynamics. Four groups of rats (n = 8 per group) received one of the following pretreatments for two weeks: none, alcohol (10% v/v in drinking water), cocaine (15 mg/kg/day ip), and alcohol+cocaine (10% v/v in drinking water + 15 mg/kg/day ip). On the day of the experiment, cocaine was administered (30 mg/kg, ip) to each rat, either alone or in combination with alcohol (5 g/kg, po), in a balanced crossover experimental design. Plasma and brain ECF concentrations of cocaine and its three metabolites: benzoylecgonine, norcocaine, and cocaethylene were assayed by HPLC-UV. The percent change in brain dopamine concentration, mean arterial blood pressure, and heart rate were determined simultaneously. A sigmoid-E(max) model was used to describe the brain cocaine concentration-neurochemical effect (dopamine) relationship, and an indirect pharmacodynamic response model was used to describe the plasma cocaine concentration-cardiovascular effect relationships. Alcohol pretreatment led to significant increase in cocaine AUC(p), alpha(t1/2), and beta(t1/2). Cocaine pretreatment significantly increased cocaine bioavailability, absorption rate constant, TBC, and the formation clearance of cocaethylene. Acute alcohol coadministration with cocaine increased cocaine AUC(p) and bioavailability, reduced the fraction of cocaine dose converted to benzoylecgonine, and increased the formation of norcocaine. These results indicate that the pharmacokinetics of cocaine, either administered alone or in combination with alcohol, is significantly altered due to prior cocaine and/or alcohol use. Both cocaine and alcohol pretreatments increased the E(max) for dopamine, with no effect on the EC(50). Acute alcohol coadministration with cocaine significantly increased the E(max) for dopamine and reduced the EC(50). Cocaine pretreatment significantly decreased the I(max) for blood pressure, IC(50), and R(max). For the heart rate response, both alcohol and cocaine pretreatments significantly increased the IC(50), with no effect on I(max). These results indicate that both cocaine and alcohol pretreatments as well as acute alcohol coadministration lead to significant alterations in cocaine pharmacodynamics that are due, at least in part, to the changes in cocaine pharmacokinetics. If similar effects occur in humans, chronic cocaine and alcohol abusers may respond differently to cocaine administration compared to naïve users and may be at higher risks of cocaine central nervous system toxicity.

Algorithms↗

PubMed2000

Carbamazepine for cocaine dependence.

BACKGROUND: Cocaine dependence has become a substantial public health problem, developing a significant number of medical, psychological and social problems, including the spread of infectious diseases (e.g. AIDS, hepatitis and tuberculosis), crime, violence and neonatal drug exposure. Although there is no consensus regarding how to treat cocaine dependence, effective pharmacotherapy has a potentially major role to play as part of a broader treatment milieu. The anti-convulsant carbamazepine, a tricyclic medication that is widely used to treat a variety of neurological and psychiatric disorder, has also been used for treatment of cocaine dependence, although its effectiveness has not been established. OBJECTIVES: To determine whether carbamazapine (CBZ) is effective on the treatment of cocaine dependence. SEARCH STRATEGY: Electronic searches of Cochrane Library, EMBASE, MEDLINE, PsycLIT, Biological Abstracts and LILACS; scan of reference list of relevant articles; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence. SELECTION CRITERIA: The inclusion criteria for all randomised controlled trials were that they should focus on the use of carbamazepine drugs versus placebo on the treatment of cocaine dependence. Trials including patients with additional diagnosis such as opiate dependence were also eligible. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently and Odds Ratios, weighted mean difference and number needed to treat were estimated. Qualitative assessments of the methodology of eligible studies were carried out using validated checklists. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. Where possible analysis was carried out according to the "intention to treat" principles. MAIN RESULTS: 5 studies were included in the review, with 455 people randomised. No differences were found regarding positive urine sample for cocaine metabolites. Scores on Spielberg State Anxiety Inventory slightly favoured carbamazepine, but didn't reach statistical significance. Dropouts were high in both groups up to 70% in the placebo group. Less dropout occurred in the Carbamazepine group (RR 0.87 95%CI 0.71-1.06). When no retention in treatment was due to side effects no differences were found. The number of participants presenting at least one side effect, reported in Kranzler (1995), was higher in the carbamazepine group (RR 4.33 95% CI 1.45-12.91). REVIEWER'S CONCLUSIONS: There is no current evidence supporting the clinical use of CBZ in the treatment of cocaine dependence. Larger randomised investigation must be considered taking into account that these time-consuming efforts should be reserved for medications showing more relevant and promising evidence.

Anticonvulsants↗

PubMed2003

Epidemiological estimates of risk in the process of becoming dependent upon cocaine: cocaine hydrochloride powder versus crack cocaine.

RATIONALE: To estimate the risk of experiencing clinical features of cocaine dependence within 1-2 years of starting cocaine use, and to examine whether crack smoking might increase this risk. METHODS: A national sample of recent-onset cocaine users was identified within public data files of the National Household Surveys on Drug Abuse (NHSDA) for the years 1995 through 1998. The sample included 572 recent-onset users of cocaine HCl powder but not crack, and 190 recent-onset users of crack, some of whom had also started use of cocaine powder no more than 23 months prior to assessment. A separate group of 93 recent-onset crack users was identified; this comparison group had started using cocaine HCl powder 2+ years before assessment. Cocaine dependence was assessed via seven standardized questions about clinical features experienced within 12 months of assessment, such as feeling unable to cut down. Multivariate response regressions were used to evaluate crack-associated excess risk and clinical profiles of cocaine dependence. RESULTS: Among persons who had recently started to use cocaine HCl powder but not crack cocaine, about 5-12% experienced clinical features of cocaine dependence. Most clinical features occurred 2-3 times more often among crack smoking users as compared to those using powder only, even with statistical adjustment for frequency of cocaine use ( P<0.01). This crack-associated excess risk is more prominent for several clinical features of cocaine dependence, including tolerance associated with cocaine use and narrowed behavioral repertoire attributed to cocaine use. CONCLUSIONS: This new epidemiological evidence suggests that crack-smoking may increase risk of cocaine dependence once cocaine use starts, but we cannot rule out the possibility that crack users start out with a greater susceptibility to become cocaine dependent.

Cocaine↗

PubMed2001

Serotonin depletion attenuates cocaine seeking but enhances sucrose seeking and the effects of cocaine priming on reinstatement of cocaine seeking in rats.

RATIONALE: Acute serotonin (5-HT) depletion by the tryptophan hydroxylase inhibitor, para-chlorophenylalanine, attenuates cocaine seeking in rats. OBJECTIVE: The present study examined the effects of chronic 5-HT depletion on cocaine- and sucrose seeking using the 5-HT-selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). METHODS: Separate groups of rats were trained to lever press for cocaine infusions (0.33 mg/kg/0.1 ml, i.v.) or for sucrose pellets (45 mg Noyes) on a fixed ratio (FR) 1 schedule of reinforcement during daily 2-h sessions. Subsequently, animals received i.c.v. infusions of either vehicle or 5,7-DHT (150 microg/6 microl or 200 microg/20 microl). After a minimum of 10 days post-lesion, cocaine- and sucrose seeking were measured as lever presses in the absence of reinforcement (extinction). Some cocaine-trained animals were also assessed for the re-establishment of self-administration and reinstatement of extinguished cocaine seeking by i.v. cocaine priming injections and response-contingent presentations of cocaine-paired stimuli. RESULTS: 5-HT depletion by the 150 microg/6 microl dose of 5,7-DHT failed to alter cocaine- and sucrose seeking despite producing a 42-77% depletion of 5-HT in limbic terminal regions. The 200 microg/20 microl dose of 5,7-DHT attenuated cocaine seeking but enhanced sucrose seeking during extinction and produced a 55-85% depletion of 5-HT. In addition, cocaine-paired cues and cocaine priming reinstated cocaine-seeking behavior, and responding was enhanced in 5,7-DHT-treated animals relative to vehicle-treated controls at the 1 mg/kg/0.1 ml priming dose. However, re-establishment of cocaine self-administration was not altered by 5,7-DHT. CONCLUSION: The results suggest that 5-HT depletion may attenuate cocaine seeking but may enhance sucrose seeking when animals are tested during extinction. Furthermore, 5-HT depletion may enhance cocaine seeking produced by cocaine itself. Together these findings suggest that 5-HT depletion may have opposite effects on incentive motivation for cocaine during abstinence versus relapse.

5,7-Dihydroxytryptamine↗

PubMed2004

Cocaine seeking over extended withdrawal periods in rats: different time courses of responding induced by cocaine cues versus cocaine priming over the first 6 months.

RATIONALE AND OBJECTIVES: We previously found time dependent increases, or incubation, of cocaine seeking induced by re-exposure to cocaine cues over withdrawal periods of up to 3 months. Here, we studied cocaine seeking induced by re-exposure to cocaine cues or cocaine itself over an extended withdrawal period of 6 months. METHODS: Rats were trained to self-administer intravenous cocaine for 6 h/day for 10 days. Cocaine seeking induced by re-exposure to cocaine cues or cocaine itself, as measured in extinction or drug-induced reinstatement tests, respectively, was then assessed 1 day, or 1, 3 or 6 months after withdrawal. Rats were first given six 1-h extinction sessions wherein lever presses resulted in contingent presentations of cues previously paired with cocaine infusions. Subsequently, reinstatement of drug seeking induced by cocaine injections (expt 1: 0, 5, and 15 mg/kg, i.p.; expt 2: 0, 2.5, and 5 mg/kg) was assessed during three 1-h sessions. RESULTS: Profound time dependent changes in responsiveness to cocaine cues in the extinction tests were observed, with low responding after 1 day, high responding after 1 and 3 months, and intermediate responding after 6 months of withdrawal. In contrast, no significant time dependent changes in cocaine-induced drug seeking were found; acute re-exposure to cocaine effectively reinstated responding at all withdrawal periods. CONCLUSIONS: Results indicate that the withdrawal period is a critical modulator of drug seeking provoked by re-exposure to cocaine cues, but not cocaine itself. Results also indicate that while the incubation of responsiveness to cocaine cues is a long lasting phenomenon, it is not permanent.

Animals↗

PubMed1995

Effects of cocaine, cocaine metabolites and cocaine pyrolysis products on the hindbrain cardiac and respiratory centers of the rabbit.

Hemodynamic and respiratory effects of vertebral artery or i.v. administration of cocaine, cocaine metabolites and cocaine pyrolysis products were measured in anesthetized rabbits. Vertebral artery administration of 1 mg of cocaine produced decreases in blood pressure and heart rate and respiratory arrest. Cocaethylene (1 mg), a cocaine metabolite produced following co-administration of cocaine and ethanol, had comparable effects except that the respiratory arrest following cocaethylene had a longer duration of action than did cocaine. A decrease in blood pressure was also observed following 1 mg of norcocaine; however, unlike cocaine, norcocaine did not affect respiration. Acute tolerance was not observed to any of the effects of 1 mg of cocaine, cocaethylene or norcocaine following vertebral artery administration. None of these compounds had significant effects following i.v. administration of the same dose. The cocaine metabolites benzoylecgonine and ecgonine methyl ester were without effect by either route in doses up to 3 mg. In contrast to cocaine, the cocaine pyrolysis products anhydroecgonine methyl ester (3 mg) and noranhydroecgonine methyl ester (3 mg) produced similar effects via both routes of administration. Both compounds produced decreases in blood pressure and heart rate and an increase in respiratory rate. Anhydroecgonine ethyl ester (3 mg), a metabolite hypothetically formed from the cocaine pyrolysis product in individuals co-administering ethanol, had effects similar to the other pyrolysis products, although its effects were not as prominent via the i.v. route of administration. Acute tolerance was observed upon administration of the cocaine pyrolysis products. These results indicate that the cocaine pyrolysis products do not share a common mechanism of action with either cocaine or the cocaine metabolites.

Animals↗

PubMed1999

Ketoconazole does not block cocaine discrimination or the cocaine-induced reinstatement of cocaine-seeking behavior.

Ketoconazole is an FDA-approved antifungal agent that also blocks the synthesis of adrenocorticosteroids and functions as a glucocorticoid receptor antagonist. It has been previously demonstrated that this drug blocks the stress-induced reinstatement of cocaine-seeking behavior and reduces low-dose cocaine self-administration in rats. In the present experiments, the effects of ketoconazole on the cocaine-induced reinstatement of extinguished cocaine-seeking behavior and on cocaine discrimination were investigated in male Wistar rats. In rats trained to self-administer cocaine (0.5 mg/kg/infusion) by pressing a lever under a fixed-ratio 4 schedule of reinforcement, cocaine (5-20 mg/kg, IP) dose dependently reinstated cocaine-seeking behavior following at least 10 days of extinction, during which responding on the cocaine lever resulted in no programmed consequences. Ketoconazole (50 mg/kg, IP) failed to block cocaine-induced reinstatement despite blocking cocaine-induced increases in plasma corticosterone. Ketoconazole (25 or 50 mg/kg) also failed to block cocaine discrimination in rats trained to discriminate 10 mg/kg cocaine from saline. In these rats, generalization to the training dose of cocaine was observed in the absence of increases in plasma corticosterone. The results of these experiments indicate that corticosterone may mediate the effects of stressors on cocaine-seeking behavior but not the direct effects of cocaine itself.

Animals↗

PubMed1992

Differential toxicity of cocaine and its isomers, (+)-cocaine and (-)-psi-cocaine, is associated with stereoselective hydrolysis by hepatic carboxylesterases in cultured rat hepatocytes.

Cocaine induces acute lethal cell injury in rat hepatocytes following N-oxidative metabolic activation by cytochrome P450-dependent and flavin-dependent monooxygenases. Beside this oxidative bioactivation pathway, hepatic carboxylesterases may cleave the carboxymethylester or the benzoylester linkage which leads to molecules found to be non-toxic in vivo. To elucidate the structural requirements of the cocaine molecule for its bioactivation and inactivation, the cytotoxic potential of the natural (-)-cocaine relative to two isomeric forms, (+)-cocaine* (the unnatural enantiomer) and (-)-psi-cocaine (the C2 epimer of the unnatural cocaine) were investigated. Primary short-term cultures of rat hepatocytes obtained from phenobarbital (PB)-pretreated rats were exposed to the drugs for up to 24 h. (-)-Cocaine produced marked time- and concentration-dependent release of lactate dehydrogenase (LDH) into the extracellular medium, whereas the other forms were not cytotoxic (0-1 mM). Furthermore, depletion of cellular glutathione (GSH) with diethylmaleate enhanced LDH release in (-)-cocaine-treated cells and caused marginal cytotoxicity in hepatocytes exposed to the other isomers. To investigate the mechanisms that could be responsible for these isomer-specific effects, the time-dependent metabolic degradation was determined both in cultured hepatocytes and in hepatic microsomes in the presence or absence of the serine carboxylesterase inhibitors, phenylmethylsulfonylfluoride (PMSF) or NaF. All three cocaine analogs were enzymatically degraded, but the rates of ester cleavage greatly varied among the stereoisomers. (-)-Cocaine was primarily N-oxidized via SKF-525A-sensitive pathways, whereas (+)-cocaine was predominantly hydrolyzed by PMSF-sensitive carboxylesterases. In contrast, (-)-psi-cocaine, which is very stable in the absence of cells at 37 degrees C and pH 7.4, was subject to extremely fast enzymatic ester cleavage. In conclusion, these results indicate that the isomer-specific differential cytotoxicity of (-)-cocaine, (+)-cocaine and (-)-psi-cocaine in hepatocytes may be related to stereoselective differences in the rates of hydrolytic inactivation by hepatic carboxylesterases and that the N-oxidative pathway, resulting in hepatocyte injury, may thus be relevant only for (-)-cocaine.

Animals↗

PubMed2003

Prediction of treatment outcome by baseline urine cocaine results and self-reported cocaine use for cocaine and opioid dependence.

This study examined the usefulness of baseline cocaine urine toxicology results and self-reported days of cocaine use in predicting treatment response in cocaine- and opioid-dependent subjects. Ninety-nine male and 52 female subjects, maintained on buprenorphine, participated in a 24-week, randomized, double-blind, four-cell trial that evaluated desipramine (150 mg/d) or placebo plus contingency management or a noncontingent voucher control. Out of 151, 102 (67%) subjects had cocaine-positive and 49 (32%) cocaine-negative urines at the beginning of treatment. For the previous 30 days before study participation, 91 (60%) subjects reported using cocaine 15 or less days (low baseline cocaine use) and 60 (40%) subjects reported more than 15 days (high baseline cocaine use). By using the treatment effectiveness score (TES) as the outcome measure, a negative urine for cocaine at baseline predicted a better outcome during a 24-week trial for cocaine and opioid use. There also was a significant interaction between baseline cocaine urine results and desipramine response with the urine cocaine-negative group showing greater desipramine response than placebo for opioid and cocaine use. Self-reported cocaine use at baseline did not show significant predictive power for TES scores during the clinical trial. These results suggest that baseline cocaine urine results should be considered as stratifying variables in clinical trials for cocaine dependence.

Adult↗

PubMed2000

Chronic continuous cocaine infusion in rats: effect on urine cocaine, ecgonine methylester and benzoylecgonine concentrations and bolus-dose cocaine pharmacokinetics.

The aim of this study was to determine the effect of chronic cocaine infusion on urine cocaine, ecgonine methylester and benzoylecgonine concentrations to establish if they varied with dose and duration of cocaine administration. Male rats were continuously infused with cocaine at either 6 or 18 mg kg(-1) daily for 13 days. Three urine samples taken over the course of the infusion period showed that cocaine, ecgonine methylester and benzoylecgonine concentrations varied with the dose administered and the duration of administration. Cocaine, ecgonine methylester and benzoylecgonine concentrations were 2-3 times greater in the high-dose group than the low-dose group at each sampling time point. These decreased, respectively, from 7.0+/-1.1, 26.7+/-4.5 and 29.5+/-5.4 microg mL(-1) to 2.5+/-0.5, 10.5+/-1.8 and 11.8+/-1.5 microg mL(-1) in the high-dose group and from 1.0+/-0-2, 7.8+/-1.5 and 6.3+/-0.1 microg mL(-1) to 0.5+/-0.1, 4.0+/-0.6 and 3.1+/-0.4 microg mL(-1) in the low-dose group (P < 0.05) over the infusion period. We also studied the pharmacokinetic and metabolic profile of an intravenous bolus dose of 2.5 mg kg(-1) cocaine hydrochloride after a similar cocaine infusion in rats. Cocaine pharmacokinetics and the profile of ecgonine methylester, benzoylecgonine and norcocaine were no different from rats chronically infused with saline for the same period. Altered cocaine metabolism could not explain the effect of the duration of cocaine infusion on altered metabolite concentrations in urine. Ecgonine methylester/benzoylecgonine urine concentration ratios did not alter with duration of infusion (1.2+/-0.2 and 1.1+/-0.2 in the high-dose group at the first and last time point) and were not affected by the dose of cocaine (1.3+/-0.6 and 1.2+/-0.1 at corresponding times in the low-dose group (P > 0.05)). We conclude that chronic cocaine infusion does not alter cocaine metabolism. This was not reflected by absolute cocaine metabolite urine concentrations, which varied with time, but was represented by urine ecgonine methyl ester/benzoylecgonine concentration ratios.

Anesthetics, Local↗

PubMed2000

Illicit cocaine use patterns in intravenous-naive cocaine users following investigational intravenous cocaine administration.

This study evaluated whether cocaine use patterns changed following investigational intravenous cocaine administration to intravenous-naive cocaine users. Subjects were respondents to a follow-up survey who had participated in one to three intravenous double-blind cocaine (0.2 or 0.4 mg/kg) administration studies. The group included healthy men (n = 17) and women (n = 8) with histories of occasional cocaine use (lifetime self-reported use of 12+/-12 (mean +/- S.D.) exposures, primarily via nasal insufflation) who were recontacted an average of 39 weeks (range 7-107 weeks) after study participation. The recontacted group constituted 45% of the total eligible sample of 55 subjects. Baseline demographics for the recontacted and non-recontacted (n = 30) samples were similar, suggesting that the recontacted sample was representative of the group as a whole. Investigational cocaine exposure did not induce adverse health events in any subject. Self-reported cocaine use estimates obtained at follow-up were compared to baseline estimates obtained with identical questionnaires and were highly concordant (Spearman rank correlation p = 0.52 and 0.78, respectively; P < 0.02 and < 0.0002, respectively). This suggests that participants provided stable and reliable reports of cocaine use. No subject reported either illicit intravenous cocaine use or altered frequency of illicit cocaine use by the customary route after investigational intravenous cocaine exposure. These data suggest that illicit cocaine use frequencies and routes of administration are not altered following investigational intravenous cocaine administration to healthy, occasional cocaine users.

Adult↗

PubMed2005

Acute and chronic cocaine behavioral effects in novel versus familiar environments: open-field familiarity differentiates cocaine locomotor stimulant effects from cocaine emotional behavioral effects.

Cocaine is a potent stimulant drug, but its stimulant effects can be substantially modulated by environmental novelty versus familiarity. In this report, we varied exposures to a novel environment as a way to assess the impact of environmental familiarity versus novelty upon the locomotor activation induced by acute and chronic cocaine treatments. In experiment 1, the effects of 1 (PE1) versus 0 (PE0) pre-exposures to the test environment were compared for their impact upon the locomotor stimulant, central zone entry and grooming effects induced by an acute cocaine (10 mg/kg) treatment. In experiment 2, the effects of 10 (PE10) versus 0 (PE0) pre-exposures upon the cocaine effects were compared. Experiment 3 assessed the effects of nine cocaine treatments (10.0 mg/kg) initiated in a novel environment (PE0) versus familiar environment (PE10). In all experiments, cocaine had a potent locomotor stimulant effect in a novel environment, which was attenuated by environmental familiarity such that in PE10 groups, cocaine did not reliably induce an acute locomotor stimulant effect. Environmental novelty/familiarity, however, did not reliably alter cocaine effects upon central zone penetration, grooming behavior, or the neurochemical effects induced by cocaine. In the chronic treatment regimen, the PE0 group exhibited a tolerance-like decrease in locomotor activation, but the PE10 group exhibited a sensitization-like increase in locomotor activation. Despite the marked directional changes in the locomotor stimulant effects of cocaine treatments, initiated in a novel (PE0) versus familiar (PE10) environment, the same asymptotic levels of locomotor activation were achieved. In contrast, the behavioral measures of central zone activity progressively increased with repeated treatments regardless of whether the environment was initially novel (PE0) or familiar (PE10). Thus, habituation factors can profoundly alter the locomotor stimulant effects of cocaine and can induce pseudo-tolerance phenomena. In contrast, central zone activity undergoes sensitization-like effects independent of habituation state and therefore appears to represent a more fundamental behavioral effect of cocaine. In that, central zone penetration in an open-field is linked to emotional processes; this finding is of substantial importance in understanding the effects of repeated cocaine usage.

Acute Disease↗

PubMed2006

Concurrent use of alcohol and cocaine: differences in patterns of use and problems among users of crack cocaine and cocaine powder.

AIM: To investigate differences in alcohol and drug consumption behaviours and related problems among users of cocaine powder versus crack cocaine. METHODS: The sample of concurrent users of alcohol and cocaine (n = 102) was recruited from clinical and community (non-clinical) settings in London. Those recruited in the community were contacted by means of snowball sampling methods. Data were collected by means of face-to-face structured interviews. RESULTS: Heavy drinking was common. There were differences in alcohol consumption between users of cocaine powder and crack cocaine. Cocaine powder users reported more frequent heavy drinking than crack users. Heavy drinking often involved drinking excessive amounts over prolonged periods. Crack cocaine users reported more serious problems associated with cocaine, other illicit drugs, psychological and physical health problems, and acquisitive crime. CONCLUSIONS: Frequent heavy drinking represents a serious risk to the health of many cocaine users. The differences in alcohol consumption patterns confirm the importance of distinguishing between use of cocaine powder and crack cocaine. Few of the sample had received treatment for cocaine or alcohol problems. Healthcare professionals working in primary care or accident and emergency settings may need to be trained to detect, assess, and respond to concurrent alcohol and cocaine problems.

Adult↗

PubMed2002

Differential effects of the 5-HT(2A) receptor antagonist M100907 and the 5-HT(2C) receptor antagonist SB242084 on cocaine-induced locomotor activity, cocaine self-administration and cocaine-induced reinstatement of responding.

These studies investigated the effects of antagonists selective for the 5-HT(2A), 5-HT(2B), or 5-HT(2C) receptor subtypes on behaviors elicited or maintained by cocaine. The selective 5-HT(2A) receptor antagonist M100907 (0.5 mg/kg, SC) attenuated the locomotor activity elicited by 10 mg/kg cocaine, whereas the selective 5-HT(2C) receptor antagonist SB242084 (0.5 mg/kg IP) potentiated the locomotor stimulant effect of 10 mg/kg cocaine. The selective 5-HT(2B) antagonist SB215505 (3 mg/kg PO) did not alter cocaine-induced locomotor activity. In a second series of experiments, the effects of M100907 and SB242084 were examined in rats self-administering cocaine intravenously according to a progressive ratio schedule. M100907 (0.5-2 mg/kg) did not alter responding for cocaine at an infusion dose of 0.25 mg. Similarly M100907 (0.5 mg/kg) failed to alter responding for cocaine at infusion doses of 0.0625, 0.125 and 0.25 mg. SB242084 (0.5-1 mg/kg) increased responding for cocaine with the infusion dose set at 0.125 mg. Examination of the effects of SB242084 (0.5 mg/kg) on the cocaine dose response curve revealed significant increases in responding at the lowest doses of 0.0625 and 0.125 but not 0.25 mg. After completion of the self-administration experiments responding was extinguished. M100907 (0.5 mg/kg) attenuated the ability of experimenter administered cocaine (10 mg/kg and 20 mg/kg) to reinstate lever pressing, whereas the priming effect of cocaine (10 mg/kg) was enhanced by SB242084. These results indicate distinct, and in some cases opposite, effects of a 5-HT(2A) compared with a 5-HT(2C) receptor antagonist on various cocaine-mediated behavioral effects.

Aminopyridines↗

PubMed2002

Reinstatement of cocaine seeking in 129X1/SvJ mice: effects of cocaine priming, cocaine cues and food deprivation.

RATIONALE AND OBJECTIVES: The mechanisms underlying relapse to cocaine seeking induced by exposure to priming cocaine injections, cues associated with cocaine self-administration and environmental stressors have been studied in rats. Here we describe a reinstatement method for studying relapse to cocaine seeking in mice, a suitable species for studying the effect of genetic manipulations such as gene knockout or gene over-expression on compulsive drug use. METHODS: Male mice of the 129X1/SvJ strain were trained for 14-16 days to self-administer cocaine (0.75 mg/kg/infusion; 4 h/day; fixed-ratio-1 schedule of reinforcement; infusions were paired with a light-tone compound cue). Next, the lever-pressing behavior was extinguished by removing the cocaine syringes in the presence (Exps. 1 and 3) or absence (Exp. 2) of the cocaine cue. Subsequently, tests for reinstatement were conducted after exposure to priming injections of cocaine (0, 1.5, 3.0 and 6.0 mg/kg, IV; Exp. 1), response-contingent presentations of the cocaine-associated cue (Exp. 2), or food deprivation stress (1 and 22 h; Exp. 3). RESULTS: The effect of cocaine priming on reinstatement was modest and was only observed at the highest dose tested. On the other hand, reinstatement of cocaine seeking was observed following exposure to the cocaine-associated cue and food deprivation stress. CONCLUSIONS: The present data suggest that factors contributing to relapse to drugs can be studied in the reinstatement model using the common 129X1/SvJ mouse inbred strain.

Animals↗