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PubMed2005

Enhanced acquisition of cocaine self-administration in rats developmentally exposed to lead.

The rate of acquisition of drug self-administration may serve as a predictor of later drug-taking behavior, possibly influencing the vulnerability to use drugs. The present study examined the effects of perinatal (gestation/lactation) lead exposure on adult rates of acquisition of intravenous cocaine self-administration using an automated procedure that included both Pavlovian and operant components. For Experiment 1, female rats were gavaged daily with 0 or 16 mg lead for 30 days prior to breeding with nonexposed males. Metal administration continued through pregnancy and lactation and was discontinued at weaning (postnatal day (PND) 21). Animals born to control or lead-exposed dams subsequently were tested daily as adults in a preparation where sessions included an initial 3-h autoshaping period followed by a 3-h self-administration period where 0.20 mg/kg cocaine was delivered contingently. During autoshaping, intravenous cocaine infusions were paired with the extension and retraction of a lever, while infusions occurred during self-administration only when a lever press was executed (FR-1). The criterion for acquisition was a 2-day period during which a mean of 50 infusions/session occurred during self-administration. Animals were given 35 days to reach criterion. In Experiment 1, accelerated rates of acquisition of cocaine self-administration were evident for lead-exposed animals relative to controls. Overall, the number of self-administered cocaine infusions per session was significantly higher for lead-exposed rats as compared to control rats. Experiment 2 replicated Experiment 1 except that a higher dose of cocaine (0.80 mg/kg) was employed as the reinforcer, and 30 infusions/session was the set criterion. At the higher cocaine dose (Experiment 2), acquisition rates for control and lead-exposed animals were not markedly different, and significantly different infusion rates were not observed.

Anesthetics, Local↗

PubMed2001

Effect of naloxone on appetitive and consummatory phases of ethanol self-administration.

BACKGROUND: The opioid system has been implicated in ethanol self-administration. Morphine, an opiate agonist, can sometimes increase the amount of ethanol consumed, and opiate antagonists such as naloxone and naltrexone decrease the amount of ethanol consumed in both animals and humans. The objective of this study was to examine the effect of naloxone on appetitive (or seeking) and consummatory behaviors by using an operant model developed to separate these two phases of self-administration. METHODS: Intraperitoneal injections of naloxone (0.3-10 mg/kg) or vehicle were given before operant self-administration sessions to assess the effect on lever pressing (appetitive behavior) and subsequent consumption. Effects were measured in two groups of rats: one self-administered a 3% sucrose solution and the other a 10% ethanol solution. RESULTS: Naloxone dose-dependently decreased ethanol and sucrose consumption by an earlier cessation of drinking in the session compared with vehicle injection days. There were some effects on appetitive responding after treatment with naloxone, but none was statistically significant. CONCLUSIONS: Naloxone may decrease ethanol self-administration by decreasing the postingestive or pharmacological effects of alcohol. This model provides a new method for examining the effects of potential pharmacotherapeutics on alcohol self-administration behavior.

Alcohol Drinking↗

PubMed2001

Treatment regimen and hypnotic self-administration.

RATIONALE AND OBJECTIVES: Previous studies have shown that insomniacs self-administer hypnotics at high nightly rates. This study determined whether prior experience with different treatment regimens (i.e., instructions and capsule availability) would alter the previously observed high hypnotic self-administration rates. METHODS: Sixty-four healthy men and women with (n = 32) and without (n = 32) insomnia, 21-55 years, self administered placebo or triazolam (0.25 mg) after different prior treatment regimens. They received one of three different treatment regimens enforced for 11 nights: a capsule each night, a capsule as needed, or a capsule every third night. On 14 subsequent nights they choose to self-administer a capsule or not, placebo during 1 week and triazolam (0.25 mg) the other (counterbalanced in order). RESULTS: Insomniacs self-administered more capsules than normals and triazolam was self-administered more than placebo. For both groups, treatment regimen had a minimal effect on capsule self-administration. During the treatment phase, triazolam improved self-ratings of sleep relative to placebo. During the choice phase, nightly variations in self-rated sleep predicted self-administration of a capsule on the following night, regardless of whether the capsule was active drug or placebo. CONCLUSIONS: The data of this study are consistent with the view that hypnotic self-administration by insomniacs is therapy-seeking behavior and not drug abuse.

Adult↗

PubMed1988

Oral ethanol self-administration in free-feeding rhesus monkeys.

The ability of a conditioning procedure to establish oral ethanol self-administration in free-feeding rhesus monkeys was assessed. The conditioning procedure required the monkey to drink an ethanol solution in order to have access to a sweet orange-flavored solution. Following an average of 14 sessions under these conditions, the orange solution was no longer delivered and ethanol solution alone was made available in the sessions. During both the conditioning and the ethanol self-administration portions of the experiment each monkey was required to drink an average of 0.5 g/kg ethanol per session in order to continue in the experiment. Of the nine monkeys exposed to these contingencies, five monkeys continued to self-administer ethanol after the presentation of the orange drink was discontinued. However, two of these five monkeys decreased their ethanol solution intake below 0.5 g/kg within 3 weeks after the conditioning sessions had terminated. The three monkeys that sustained high ethanol intake were male and had histories of drug self-administration, suggesting that gender and drug history may influence the initiation of ethanol self-administration. Once ethanol self-administration was established, concentrations of ethanol from 4 to 15% (v/v) were made available. The monkeys consumed intoxicating amounts of ethanol, as indicated by average intakes ranging from 0.5 to 0.9 g/kg and blood ethanol levels over 100 mg/dl. These results demonstrate that ethanol self-administration can be established and maintained through the initial reinforcement of ethanol consumption by the contingent presentation of another reinforcing stimulus. However, the results of this study also indicate that individual differences may be an important determinant of animals initiating ethanol self-administration.

Alcohol Drinking↗

PubMed1985

Effects of intracerebroventricular administration of methyl naloxonium chloride on heroin self-administration in the rat.

A quaternary derivative of naloxone, methyl naloxonium chloride (MN), was administered intracerebroventricularly (ICV) to rats trained to self-administer heroin intravenously. MN produced a dose-dependent (0.5-4.0 micrograms) increase in responding for heroin. Since MN is unlikely to reach the peripheral circulation in these doses, these results were viewed as strongly supporting the hypothesis that central opiate receptors are solely responsible for mediating the reinforcing properties of heroin during self-administration. In addition, the present study suggests that intracerebral MN injections may prove to be a useful technique in the search for central substrates of heroin reward.

Animals↗

PubMed2001

GABA mechanisms in the pedunculopontine tegmental nucleus influence particular aspects of nicotine self-administration selectively in the rat.

RATIONALE: The pedunculopontine tegmental nucleus (PPTg) is part of the neuronal circuit activated by self-administered nicotine. The cholinergic neurons of the PPTg comprise a prominent projection to midbrain dopamine neurons. However, anatomical studies of Fos expression suggest that nicotine targets primarily non-cholinergic neurons in the PPTg, especially GABAergic and glutamatergic neurons. OBJECTIVE: The objective of these experiments was to examine the role of GABA manipulations in the PPTg on nicotine self-administration. METHODS AND RESULTS: Rats trained to self-administer nicotine or cocaine intravenously were prepared with brain microcannulae directed to the PPTg. Intra-PPTg microinfusions of the GABA agonists muscimol (10-50 ng) and baclofen (30-60 ng) reduced nicotine self-administration maintained on a fixed-ratio schedule of reinforcement (30 microg/kg per infusion); self-administration of cocaine (0.3 mg/kg per infusion) under an identical schedule was not affected. Muscimol and baclofen were also examined after intra-PPTg microinfusion in animals trained to self-administer nicotine on a progressive-ratio schedule (10 and 30 microg/kg per infusion). Progressive-ratio responding was sensitive to pharmacological manipulations such as a change in the nicotine dose available for self-administration, or intra-PPTg microinfusion of the nicotinic antagonist dihydro-beta-erythroidine (30 microg). However, nicotine self-administration on a progressive-ratio schedule was not altered by intra-PPTg microinfusions of GABA agonists. CONCLUSIONS: These data confirm that the PPTg is involved in nicotine self-administration, a conclusion that is independent of the schedule of reinforcement that is used. GABAergic mechanisms in the PPTg play a selective role in nicotine reinforcement compared to cocaine, and that role is restricted to the characteristics of reinforcement measured by fixed-ratio responding.

Animals↗

PubMed1991

Evaluation of nefazodone self-administration in rhesus monkeys.

Intravenous self-administration of nefazodone, a potential new antidepressant medication, was evaluated using a substitution procedure in rhesus monkeys. Subjects had established stable rates of responding for cocaine (0.033 mg/kg per infusion) under a fixed-ratio 10 schedule during 60-min sessions each day. Various does of nefazodone hydrochloride (0.03-0.3 mg/kg per infusion) were substituted for cocaine for four consecutive daily self-administration sessions. Compared to rates of responding obtained during saline substitutions, nefazodone failed to function as a reinforcer when substituted for cocaine. In only one monkey, at one dose, did the rate of responding exceed the range of saline responding; an effect not observed in two subsequent replications in that subject. In all three monkeys, the total number of infusions tended to decrease during the 4-day nefazodone substitution and the majority of nefazodone infusions occurred during the first quarter of each session, with few infusions occurring in the latter three-quarters. Overall intake of nefazodone increased as a function of dose per infusion. Such a result is expected when response rates do not vary with dose, which is more likely to occur when a test drug is not a reinforcer. In summary, the present results provide no evidence of reinforcing effects with nefazodone and suggest that it would possess little or no abuse liability.

Animals↗

PubMed2003

Mecamylamine acutely increases human intravenous nicotine self-administration.

Previous studies of human cigarette smoking have shown that administration of the nicotinic acetylcholine receptor antagonist mecamylamine produces acute increases in smoking behavior. In contrast, studies of intravenous nicotine self-administration in animals typically show an immediate decrease in self-administration behavior following mecamylamine administration. To investigate whether this discrepancy might be due in part to the mode of nicotine self-administration (intravenous vs. cigarette smoke), we measured the rate of intravenous nicotine self-administration in tobacco-dependent human smokers. After being trained in a preliminary session to self-administer puff-sized bolus doses of nicotine, 16 subjects were exposed to two sessions (4 h duration) in which they could self-administer intravenous nicotine ad lib. Two hours prior to one session, subjects swallowed a capsule containing 10 mg mecamylamine, and before the other session they took a placebo capsule. Rates of responding for nicotine were assessed, as were subjective reports of withdrawal symptoms and plasma nicotine levels. There was a significantly higher rate of nicotine self-administration in the mecamylamine condition, and mecamylamine attenuated the reduction in craving over the session that occurred during nicotine self-administration. These results indicate that route of administration is not likely the major source of the discrepancy between findings from animal and human studies of nicotine administration. Instead, it is likely that the higher rates of nicotine self-administration induced by mecamylamine were due to an attenuation of the effects of nicotine (e.g., alleviation of withdrawal symptoms) in nicotine-dependent subjects. Thus, animal models of nicotine dependence may need to be employed in conjunction with self-administration procedures in order to duplicate the effects of mecamylamine observed in studies of human smokers.

Adolescent↗

PubMed1998

Effects of acute and chronic doses of naltrexone on ethanol self-administration in rhesus monkeys.

The effects of acute and chronic administration of intramuscular naltrexone (0.1, 0.3, 1.0, and 3.0 mg/kg) on oral ethanol (8%) self-administration were examined. Naltrexone (1.0 mg/kg) effects on the self-administration of ethanol concentrations ranging from 0.5 to 8% (w/v) were also investigated. Rhesus monkeys with substantial histories of drug and ethanol drinking served as subjects. During daily 3-hr sessions, monkeys were presented with ethanol solutions, concurrently available with water, under fixed-ratio reinforcement schedules. Naltrexone decreased the consumption of ethanol (g/kg). Biphasic temporal effects were observed within sessions. Naltrexone dose-dependently decreased the number of ethanol deliveries by a maximum of 56% (n = 18; 3 monkeys x 6 sessions) during the first hour of the session. During the second and third hours, however, ethanol intake recovered such that maximum decreases over the 3-hr session were approximately 27% (n = 18), and the mean decrease was 16% (n = 18). Often marked tolerance was observed, such that the effects of acute naltrexone administration were greater than effects after chronic administration. The self-administration of low ethanol concentrations (< or =2% w/v) was increased in several monkeys, by up to 340%, after naltrexone pretreatment. In summary, the effects of naltrexone on ethanol self-administration, in drug- and alcohol-experienced rhesus monkeys, are not characterized by unitary decreases in measures of ethanol self-administration. Rather, differential naltrexone effects were a function of experimental parameters, including the dose and number of naltrexone injections, the ethanol concentration, and the time point of measurement.

Alcohol Drinking↗

PubMed1999

Adenosine A(2) receptors inhibit morphine self-administration in rats.

In the present study, the effect of adenosine receptor agonists and antagonists on morphine self-administration was investigated. Intravenous administration of morphine (0.3-3 mg/kg/injection) induced dose-dependent self-administration. The adenosine receptor antagonists, theophylline (2.5, 5, 10 mg/kg) and 3, 7-Dimethyl-1-propargylxanthine (DMPX; 0.25, 0.5, 1 mg/kg), when injected 1 h before the start of the test, reduced the number of self-administered morphine infusions. The adenosine receptor antagonists when administered in the training period (11 days) greatly increased the number of morphine infusions, however, they did not induce any response by themselves. 5'-N-ethylcarboxamido-adenosine (NECA; 0.5, 1 mg/kg) and 4-[2-[[6-Amino-9-(N-ethyl-beta-D-ribofuranuronamidosyl)-9H-purin-2 -yl ]amino] ethyl]benzenepropanoic acid (CGS21680; 0.001, 0.01, 0.025, 0. 05 mg/kg), given 1 h before the start of the test, increased morphine self-administration. Although the adenosine agonists, when injected during training period (11 days), reduced morphine self-administration. Furthermore, NECA, but not CGS21680, induced significant self-administration. The adenosine A(1) receptor agonist, N(6)-cyclohexyladenosine (CHA; 0.01, 0.1, 0.25, 0.5 and 1 mg/kg), and the adenosine A(1) receptor antagonist, 8-phenyletheophylline (2, 4, 6, 8 mg/kg), themselves neither altered morphine infusion nor induced any response. These results indicate a role for adenosine A(2) receptors in the expression and/or development of morphine self-administration.

Animals↗

PubMed1990

Desipramine effects on cocaine self-administration by rhesus monkeys.

The effects of desipramine treatment (0.56-10.0 mg/kg per day) on cocaine self-administration were compared to saline treatment in five rhesus monkeys. Cocaine (0.050 or 0.100 mg/kg per inj) and food (1 g banana pellets) self-administration were maintained on an FR 4 (VR 16:S) reinforcement schedule. Desipramine (or an equal volume saline control solution) was infused over 1 h each day through the second lumen of an intravenous catheter. After 5 days of baseline saline treatment, seven doses of desipramine each were administered for 5 days in an ascending order. Cocaine self-administration increased (P less than 0.01) or remained equivalent to base-line levels in 4 of 5 subjects during the first 15 days of desipramine treatment (0.56 to 1.78 mg/kg per day). Three monkeys continued to self-administer cocaine equivalent to or significantly above base-line levels (P less than 0.01) during days 16-30 of desipramine treatment (3.2-7.86 mg/kg per day). The highest desipramine dose (10 mg/kg per day) significantly suppressed cocaine self-administration in only one of these three monkeys (P less than 0.01). Desipramine treatment (3.2-10.0 mg/kg per day) suppressed cocaine self-administration (P less than 0.01) without a concomitant suppression of food-maintained responding in one of five subjects. A generalized suppression of both cocaine and food-maintained responding (P less than 0.01) during desipramine treatment occurred in one monkey that took the highest base-line levels of cocaine (6.3 +/- 1.03 mg/kg per day). Food-maintained responding remained equivalent to or significantly above (P less than 0.01) base-line levels in four of five monkeys during desipramine treatment. A transient decrease in food self-administration at desipramine doses of 1.78-5.62 mg/kg per day occurred in one monkey (P less than 0.01). Thirty days of desipramine treatment at the highest doses (5.62, 7.86 and 10.0 mg/kg per day for 10 days each) also did not suppress cocaine self-administration in a monkey that took an average of 4 mg/kg per day of cocaine during saline base-line treatment. These primate data are concordant with the extant clinical literature on the inconsistent effects of desipramine treatment; i.e., both stimulation of cocaine use and inconsistent or incomplete attenuation of cocaine abuse during desipramine maintenance have been reported.

Animals↗

PubMed1996

Effect of nucleus accumbens dopamine depletion on motivational aspects involved in initiation of cocaine and heroin self-administration in rats.

The involvement of mesolimbic dopamine (DA) systems in motivational aspects of drug-taking behavior during initiation of drug self-administration was investigated using a recently developed behavioral paradigm. In separate experiments animals were allowed to self-administer cocaine or heroin (0.16 and 0.32 mg . kg-1 per inf) during 5 consecutive daily 3-h sessions. During a 15-min period preceding the last four self-administration sessions lever-press behavior was measured in absence of the drug as an index of the motivational aspects involved in drug-taking behavior. The effect of 6-hydroxydopamine (6-OHDA) lesion of the nucleus accumbens (NAC) on lever-press behavior before and during self-administration was measured. Destruction of DA terminals in the NAC did not affect initiation of heroin self-administration nor the lever-press behavior during the period preceding the self-administration sessions. In cocaine animals 6-OHDA lesion of the NAC decreased the total intake of cocaine during the self-administration sessions and impaired discriminative lever-responding for the drug, both during cocaine self-administration, and during preceding periods when no cocaine was available. It is concluded that DAergic systems in the NAC might be involved in the reinforcement and/or motivational processes underlying cocaine self-administration. The present findings, however, do not support the notion of a critical role of NAC DA in the motivational aspects of drug-taking behavior in general.

Animals↗

PubMed1994

Establishing benzodiazepines as oral reinforcers: midazolam and diazepam self-administration in rhesus monkeys.

Oral benzodiazepine self-administration was examined in four adult male rhesus monkeys with histories of ethanol- and pentobarbital-reinforced behavior. Drug solutions and vehicle were concurrently available for 3-hr each day under fixed-ratio (FR) reinforcement schedules. Initially, the monkeys rejected a midazolam solution (0.1 mg/ml) after direct substitution of the drug for an 8% ethanol solution. However, midazolam self-administration was subsequently established by using a fading procedure in which increasing amounts of drug (0.0125-0.2 mg/ml) were gradually added to an 8% ethanol solution, followed by gradual reduction of the ethanol concentration to zero. Midazolam was an effective reinforcer for three of four monkeys tested, i.e., responding that was maintained by the drug solution exceeded that maintained by the drug vehicle. The fourth monkey also self-administered midazolam but drug-maintained responding was not consistently greater than vehicle-maintained responding. The responding maintained by the drug was an inverted-U-shaped or bitonic function of midazolam concentration. The midazolam intake (in milligrams per kilogram) increased as a function of increases in the drug concentration. At the higher concentrations, marked sedative intoxication was observed. There was an inverse relationship between FR size (varied from FR 8 to FR 32) and the amount of drug self-administered. The three monkeys in which midazolam functioned as a reinforcer were then tested with diazepam (0.2 mg/ml), which maintained drug self-administration behavior on direct substitution for 0.2-mg/ml midazolam. Diazepam-maintained responding usually exceeded water responding as the diazepam concentration was increased to 0.8 mg/ml. These data demonstrate robust reinforcing effects of both "short-" and "long-acting" benzodiazepines delivered by the oral route.

Administration, Oral↗

PubMed1994

Behavioral and neurochemical sensitization following cocaine self-administration.

To determine if behavioral and neurochemical sensitization results from cocaine self-administration, rats were trained to self-administer cocaine for 20 consecutive days (26.5 +/- 2.6 mg/kg, IV/day). At 24 h or 21 days after discontinuing cocaine self-administration or yoked saline control, rats were administered an acute injection of saline IP, followed 60 min later by cocaine (15 mg/kg IP). Cocaine-induced changes in motor activity were monitored with a photocell apparatus and alterations in extracellular dopamine in the ventral striatum were measured with microdialysis. There was no difference between treatment groups in the basal level of extracellular dopamine as determined by in vitro calibration. Neither the motor stimulant response nor the increase in extracellular dopamine following an acute cocaine challenge given after 24 h of withdrawal was different between rats which self-administered cocaine and yoked saline controls. However, when the cocaine challenge was given 21 days after discontinuing cocaine self-administration both the motor response and extracellular dopamine content in the ventral straitum were significantly augmented in rats that self-administered cocaine. While no correlation was observed between the average amount of cocaine self-administered each day and the cocaine-induced alterations in extracellular dopamine at either 24 h or 21 days of withdrawl, a significant positive correlation was measured between the increase in photocell counts and the average daily cocaine administration at 21 days of withdrawl. These data show that cocaine self-administration produces an augmentation in the acute behavioral and neurochemical response to a cocaine challenge that resembles the sensitization previously demonstrated with repeated noncontingent administration.

Animals↗

PubMed1991

Drug self-administration methods in abuse liability evaluation.

The human drug self-administration paradigm is an extension of the animal model developed in the 1960s. The paradigm can be used to investigate the determinants and correlates of drug-seeking and drug-taking behavior and has proven useful in the development of medications for treating drug dependence. This paper describes the basic components of the human self-administration model and discusses studies that illustrate some of its applications, including assessment of the reinforcing effects of drugs, analysis of behavioral and pharmacological mechanisms of drug self-administration and measurement of the abuse liability, behavioral toxicity, and aversive effects of drugs. Some of the strengths and limitations of using the paradigm with human research subjects are also presented. It is concluded that the drug self-administration model should not replace other measures of abuse liability testing in humans, but should be incorporated into comprehensive programs of drug abuse assessment wherever possible.

Drug Evaluation↗

PubMed2002

Pharmacological manipulations of the pedunculopontine tegmental nucleus in the rat reduce self-administration of both nicotine and cocaine.

RATIONALE: The pedunculopontine tegmental nucleus (PPTg) has been implicated in the self-administration of drugs, particularly nicotine, which acts directly through the PPTg in addition to targeting midbrain dopamine neurons. The direct action of nicotine in PPTg may be through GABAergic mechanisms that have been shown to influence nicotine self-administration preferentially compared to cocaine. OBJECTIVE: The purpose of these experiments was to examine several pharmacological manipulations that alter neuronal activity in the PPTg for their specificity or generality in nicotine versus cocaine reinforcement. METHODS AND RESULTS: Rats trained to self-administer nicotine or cocaine intravenously were prepared with brain microcannulae directed to the PPTg. Intra-PPTg microinfusions of the muscarinic agonist carbachol (0.1-1.0 microg), the micro opioid agonist DAMGO (0.005 and 0.05 microg), tetrodotoxin (5 ng) and neostigmine (0.5 nmol) each reduced the self-administration of nicotine and cocaine maintained on an FR5 schedule of reinforcement. The muscarinic antagonist scopolamine (0.1-1.0 microg) and the opioid antagonist CTOP (1 microg) did not affect self-administration, but reversed the effects of the respective agonist when co-administered with it. Carbachol and DAMGO were also tested in self-administration maintained on a progressive-ratio schedule; each agonist again reduced both nicotine and cocaine self-administration. CONCLUSIONS: PPTg manipulations are able to alter established self-administration of nicotine, which acts at the level of the ventral tegmental area and the PPTg itself, and cocaine, which acts through the mesolimbic dopamine system. These data suggest that the PPTg is an important substrate in drug dependence.

Animals↗

PubMed1999

Expression of c-fos, NGFI-A and secretogranin II mRNA in brain regions during initiation of cocaine self-administration in mice.

Intravenous cocaine self-administration in mice was studied to find correlates of the acquisition of cocaine-oriented operant behaviour in the expression of nerve growth factor-induced clone A (NGFI-A), c-fos and secretogranin II mRNAs. Yoked control animals, receiving cocaine passively, served as controls for the neurochemical effect of non-contingent cocaine infusion. Animals controlling their cocaine infusions did more nose-pokes during a 30-min trial than yoked controls and animals receiving only saline, indicating a reinforcing effect of cocaine. Compared with saline, an increase in c-fos mRNA in lateral and basolateral amygdala was found in active cocaine-receiving animals, and a decrease in yoked controls receiving cocaine. There is previous evidence for an involvement of the amygdala, particularly its basolateral part, in cocaine's effects on motivation. In caudate putamen, both contingent and non-contingent cocaine increased c-fos mRNA. Non-contingent cocaine infusions increased NGFI-A mRNA expression in the core of nucleus accumbens, medial caudate putamen and frontal cortex, whereas self-administration eliminated these effects. In the core of the nucleus accumbens and piriform cortex there was increased, and in medial amygdala decreased secretogranin II mRNA in yoked controls compared with saline controls. In contrast, in basomedial and central nuclei of amygdala, increased secretogranin II mRNA was found in self-administering mice. Previous studies measuring gene expression after cocaine administration obviously did not give the complete picture of changes in gene expression in the drug-taking organism. As differences in c-fos and secretogranin II mRNA between active mice and yoked controls were robust, measuring these mRNAs may identify neurons selectively involved in acquisition of cocaine-taking behaviour.

Amygdala↗

PubMed2000

The failure of some rats to acquire intravenous cocaine self-administration is attributable to conditioned place aversion.

Although cocaine administration in humans includes euphoric and anxiogenic effects, the latter are less well understood. Acute cocaine administration produces aversive effects including anxiogenic effects as well as appetitive effects in rats and mice. In the present study the self-administration and conditioned place preference paradigms were used to determine whether the failure of some rats to acquire intravenous cocaine self-administration is attributable to either an interference with learning or an aversion to cocaine. Rats were classified as self-administrators or non-self-administrators based on the mean number of cocaine self-infusions per session and whether or not rats exhibited either a stable high level of responding or a stable low level of responding. Intravenously administered cocaine produced place preference for the self-administrators, while intravenously administered cocaine produced place aversion for the non-self-administrators. The fact that the non-self-administrators showed place aversion is inconsistent with the interpretation that the failure of these rats to readily self-administer is attributable to cocaine-mediated interference of learning. This is the first study in which both the self-administration and the conditioned place preference paradigms have been used in the same animals to demonstrate that the effects of cocaine are appetitive for some rats and aversive for others, and are not an artifact of cocaine's interference with learning.

Analysis of Variance↗