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Results for “Behavior, Addictive”

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At least 433 records · Page 24Linked to original sources

PubMed2005

High concentrations of plasma brain-derived neurotrophic factor in methamphetamine users.

Methamphetamine is a highly addictive drug that has a neurotoxic effect on the brain. A growing body of evidence suggests that brain-derived neurotrophic factor (BDNF) is associated with addictive behavior. The present study investigated the changes in plasma BDNF concentration that were induced by chronic methamphetamine use. Using an enzyme-linked immunosorbent assay (ELISA), we measured peripheral BDNF levels in methamphetamine users and in a control group. The plasma BDNF concentrations of methamphetamine users were significantly higher compared with those of controls (2536.3 pg/ml versus 1352.6 pg/ml). This finding suggests that BDNF plays some role in the neurotoxicity of methamphetamine.

Adult↗

PubMed2005

Activation of central neurokinin-1 receptors induces reinstatement of cocaine-seeking behavior.

A number of neurochemical systems have been implicated in mediating relapse to drug-seeking behavior. Substance P (SP) is a neuropeptide that interacts with some of these systems, suggesting a possible role for SP and its preferred receptor, the neurokinin-1 (NK-1) receptor, in the mediation of relapse. In this study, we examined whether selective activation of NK-1 receptors induces reinstatement of cocaine-seeking behavior, and whether endogenous activity at these receptors is involved in mediating cocaine-induced reinstatement. For each experiment, rats were trained to self-administer cocaine for 8--10 days, and following a period of extinction, tests for reinstatement were given. To examine the effects of NK-1 receptor activation on reinstatement of cocaine-seeking behavior, animals received an intracerebroventricular (ICV) infusion of the selective NK-1 receptor agonist, [Sar(9)Met(O(2))(11)]-SP (0, 1, 3 microg), immediately prior to the test session. To examine the role of endogenous NK-1 receptor activity on cocaine-induced reinstatement, rats were pretreated with ICV infusions of the selective NK-1 receptor antagonists, RP 67580 (0, 0.1, 0.5, 2.5 nmol) or GR 82334 (0, 2, 10, 50 pmol), prior to systemic priming injections of cocaine (10mg/kg or 20mg/kg; i.p.). The results showed that [Sar(9)Met(O(2))(11)]-SP induced reinstatement of cocaine-seeking behavior, but that RP 67580 and GR 82334 had no effect on cocaine-induced reinstatement. These findings suggest that while activation of NK-1 receptors is capable of inducing reinstatement of cocaine-seeking behavior, endogenous activity at these receptors is not involved in mediating the priming effects of cocaine on reinstatement of drug-seeking behavior.

Animals↗

PubMed2004

Impulsivity in youth predicts early age-related cognitive deficits in rats.

Impulsivity is a feature of psychiatric disorders such as mania, addictive behaviors or attention deficit-hyperactivity disorder (ADHD), which has recently been related to complaints of forgetfulness in adults. We investigated whether impulsiveness exerts a long-term influence on cognitive function in rats in a longitudinal study. Impulsivity, assessed by the ability to complete a sequence of presses to obtain food (conditioning box), spatial working memory (8-arm radial maze) assessed with varying degree of attentional load and recognition memory (Y-maze) were tested at different ages. Marked individual differences in impulsivity were observed at youth and remained stable at middle-age despite a general decline in the trait. Working memory scores of impulsive and non-impulsive rats did not differ in youth, whereas by middle-age the impulsive group had impaired working memory and was more sensitive to a higher attentional demand. Thus, impulsiveness in youth predicts cognitive performance in middle-age. These findings may help refine the search for early biological substrates of successful aging and for preventive follow-up of subjects at risk of impaired cognitive aging.

Age Factors↗

PubMed2005

Neural substrates of faulty decision-making in abstinent marijuana users.

Persistent dose-related cognitive decrements have been reported in 28-day abstinent heavy marijuana (MJ) users. However, the neural substrates of these decrements in cognitive performance are not known. This study aimed to determine if 25-day abstinent MJ users show persistent dose-related alterations in performance and brain activity using PET H(2)(15)O during the Iowa Gambling Task-IGT (a decision-making task). Eleven heavy MJ users and 11 non-drug users participated. The MJ group resided in an inpatient research unit at the NIH/NIDA-IRP for 25 days prior to testing to ensure abstinence. A dose-related association was found between increased MJ use and lower IGT performance and alterations in brain activity. The MJ group showed greater activation in the left cerebellum and less activation in the right lateral orbitofrontal cortex (OFC) and the right dorsolateral prefrontal cortex (DLPFC) than the Control group. When the MJ group was divided into Moderate (8-35 joints/week) and Heavy users (53-84 joints/week), the Heavy MJ group showed less activation in the left medial OFC and greater activation in the left cerebellum than the Moderate group. However, brain activity and task performance were similar between the Moderate MJ users and the Control group, suggesting a "threshold effect". These preliminary findings indicate that very heavy users of MJ have persistent decision-making deficits and alterations in brain activity. Specifically, the Heavy MJ users may focus on only the immediate reinforcing aspects of a situation (i.e., getting high) while ignoring the negative consequences. Thus, faulty decision-making could make an individual more prone to addictive behavior and more resistant to treatment. Finally, it is unclear if these neurologic findings will become progressively worse with continued heavy MJ use or if they will resolve with abstinence from MJ use.

Adult↗

PubMed2004

Beta2-subunit-containing nicotinic acetylcholine receptors are critical for dopamine-dependent locomotor activation following repeated nicotine administration.

Activation of the mesolimbic dopamine system is a critical component underlying addictive behaviors, including smoking. It has been hypothesized that the initial effect of nicotine on the dopamine system is to activate high affinity nicotinic acetylcholine receptors (nAChRs) containing the beta2 subunit, but that these receptors rapidly desensitize and are not critical for ongoing dopaminergic activation. To clarify the role of beta2-subunit-containing (beta2*) nAChRs in activation of the dopamine system and subsequent locomotor activation by repeated nicotine administration, C57BL/6J (B6) mice were administered 200 microg/ml of nicotine in the drinking water and the onset of locomotor activation was measured. B6 mice showed an increase in locomotor activity in response to chronic nicotine which was blocked by oral administration of the dopamine receptor antagonist pimozide. Knockout mice lacking the beta2 subunit of the nAChR did not show locomotor activation in response to chronic nicotine exposure, suggesting that beta2* nAChRs are critical for ongoing activation of the dopamine system by chronic nicotine administration and the resulting locomotor activation in mice.

Animals↗

PubMed2005

Spontaneous individual differences in cognitive performances of young adult rats predict locomotor response to amphetamine.

Inter-individual differences in cognitive capacities of young adult rats have largely been ignored. To explore this variability and its neurobiological bases, the relationships between individual differences in working memory and locomotor responses to novelty and to amphetamine were investigated in SD rats. Groups of good and poor learners were isolated, the latter demonstrating a markedly slower learning of the task compared to performant rats, with more perseverations independently to motivational state. They also presented a much higher increase in amphetamine-induced locomotion that remained significant for more than 1h after the injection. These results provide evidence that variability in cognitive capacities can be used to reveal their neurobiological substrates. They open new perspectives to study a possible cognitive origin of addictive behaviors and to investigate the involvement of these inter-individual differences on those observed later in life.

Age Factors↗

PubMed2004

Social crowding sensitizes high-responding rats to psychomotor-stimulant effects of morphine.

Large individual differences have been identified toward varied addictive effects as evidenced in self-administration, place conditioning, and psychomotor stimulation paradigms, which have been primarily attributed to the role of congenital factors. However, it remains unknown whether environmental factors, like extraneous social stress events, could distinctively modulate animals with differentiated biobehavioral traits, such as rats with higher motor activity (high responder, HR) developed in a novel environment and their counterparts, LR (low responder) rats. In the present study, the influence of social crowding procedure upon morphine psychomotor effect was investigated. Moreover, the roles social stress played, respectively, on HRs and LRs were explored based on previous observation that HRs not only responded more to drugs but also to stress. Our results revealed that social crowding procedure could sensitize morphine psychomotor effect as a whole, and this effect was only evident for HR but not LR rats. The individual differences toward morphine psychomotor effects was indiscernible in rats housed in normal social conditions and only turned out to be significant under stress conditions. Given the fact that the occurrence of human addictive behavior usually happens within social environment permeated with various stress factors, the genetic and environmental elements may collaboratively contribute to the ultimate susceptibility of drug-prone individuals.

Animals↗

PubMed2006

Multiple substance use among young males.

Neurobiological studies hypothesize a common final pathway of addictive behavior in the mesolimbic dopaminergic system. Nicotine has been shown to sensitize the reward pathway, thereby causing increased drug-seeking behavior. Since there is evidence to suggest that nicotine, alcohol and other psychoactive substances act on the same final pathway and seem to augment their effects in animal subjects, drug intake behavior of humans would likely be reflected in increased substance use of nicotine-dependent persons. We used biological markers of substance use as well as questionnaires to assess the levels of psychoactive substance use among 18-year-old males in a naturalistic cross-sectional setting. We found that increasing levels of nicotine dependence were related to higher levels of alcohol abuse and dependence. Furthermore, higher levels of nicotine dependence were associated with elevated levels of recent cannabinoid use.

Adolescent↗

PubMed2005

Are nonpharmacological induced rewards related to anhedonia? A study among skydivers.

It is well-known that persons with a drug addiction experience feelings of anhedonia during "normal" daily activities. It has been proposed that these symptoms of anhedonia are the result of direct pharmacological influences of drugs on the dopamine system. To test the assumption that nonpharmacological processes are also involved in anhedonia, we studied anhedonic symptoms in skydivers who regularly expose themselves to thrillful extreme sport activity and then experience intense hedonic feelings. A group of skydivers completed anhedonia scales and their scores were compared to a control group (a group of rowers). The main finding of the present study was that subjects who engage in the high-risk activity of skydiving, experienced more anhedonic symptoms than subjects who do not engage in such an extreme sport, but rather prefer a low-risk activity like rowing. This finding supports the notion that skydiving has similarities with addictive behaviors and that frequent exposure to "natural high" experiences is related to anhedonia. This suggests that the negative emotional state as observed in drug users may not be exclusively the results of exogenous psychopharmacological effects, but might also result from psychological mechanisms that are partly responsible for these anhedonic feelings.

Adult↗

PubMed2003

Stress hormone responses to corticotropin-releasing hormone in substance abusers without severe comorbid psychiatric disease.

BACKGROUND: Preclinical data indicate a crucial role of stress in the acute effects of drugs of abuse, maintenance of self-administration, and susceptibility to relapse. Stress system activation may serve as a marker for a neurochemical dysfunction with prognostic significance in patients with addiction. METHODS: We tested pituitary adrenocorticotrophin (ACTH) and adrenal cortisol response to ovine corticotropin-releasing hormone (oCRH) to assess the reactivity of the hypothalamic-pituitary-adrenal (HPA) axis in seven nonsubstance-abusing subjects, 31 polysubstance-abusing subjects without depressive symptoms, and seven subjects with substance abuse and depressive symptoms. No subject met diagnostic criteria for depression or other severe psychiatric disease. RESULTS: Compared with normal control subjects, substance abusers showed significantly lower ACTH and cortisol responses over the course of oCRH stimulation (p <.0001). Substance abusers with depressive symptoms showed similarly blunted responses. CONCLUSIONS: Polysubstance abusers with no past or current diagnosis of other Axis I disorders show blunted ACTH and cortisol responses to oCRH administration. The finding of an activated HPA axis in this population suggests an overlapping role of central CRH and HPA axis activation in affective disorders and substance abuse, which is likely to constitute an endocrine milieu necessary for the maintenance of addictive behavior. These data support the role of future therapeutic trials with nonpeptide CRH receptor 1 antagonists in these patients.

Adrenocorticotropic Hormone↗

PubMed1997

Allelic association of a dopamine transporter gene polymorphism in alcohol dependence with withdrawal seizures or delirium.

Hereditary factors confer susceptibility to alcohol dependence. Alcohol mediates its reinforcing effects by enhancing dopamine activity in the mesolimbic dopamine system. The role of the dopamine transporter in terminating dopaminergic activity in synaptic neurotransmission suggests that variants of the dopamine transporter gene (DAT1) might contribute to individual differences in vulnerability to addictive behavior. Our population-based association study investigated whether variants of DAT1 confer susceptibility to alcohol dependence in 293 alcoholics and clinically more homogeneous subgroups formed by: positive family history, early age-at-onset, delirium, withdrawal seizures, antisocial tendencies, type 1 and 2 alcoholics. Analyzing a VNTR polymorphism in the 3' untranslated region of DAT1, we found a significantly increased prevalence of the nine-repeat allele in 93 alcoholics displaying withdrawal seizures or delirium, compared with 93 ethnically matched nonalcoholic controls (p = 0.003; OR = 2.44; 95% confidence interval: 1.35-4.43). Our data provide evidence that a major genetic determinant of DAT1 influences vulnerability to severe alcohol withdrawal symptoms.

Adult↗

PubMed2001

Postnatal stress selectively upregulates striatal N-methyl-D-aspartate receptors in male rats.

Early life events have been thought to contribute towards vulnerability to drug addiction later in life. In the present investigation, the effect of daily neonatal maternal isolation stress on NMDA channel activity was studied. [3H]MK-801 binding was measured in several brain regions from neonatally isolated (ISO) and nonhandled (NH) adult male and female rats. Maximal [3H]MK-801 binding in the caudate-putamen of male ISO rats was 58% higher compared to same sex NH rats. Unlike male rats, maximal [3H]MK-801 binding in the caudate-putamen of female ISO rats was lower than female NH rats. No other brain region showed any significant difference in maximal [3H]MK-801 binding between ISO and NH male and female rats, respectively. There was no effect of pup isolation on the binding affinity (K(d) value) in either sex. Repeated maternal isolation is associated with alterations in the NMDA channel activity in the caudate-putamen of adult rats, and may be responsible for the augmentation in the addictive behavior reported.

Animals↗

PubMed1997

Arteriovenous differences in plasma concentration of nicotine and catecholamines and related cardiovascular effects after smoking, nicotine nasal spray, and intravenous nicotine.

BACKGROUND AND OBJECTIVES: Delivery of a high concentration bolus of nicotine through the arterial circulation is believed to be an important determinant of the addictive, behavioral, and physiologic effects of nicotine. To better understand the pharmacologic features of nicotine with different routes of administration, we measured arterial and venous plasma concentrations of nicotine, cotinine, epinephrine, and norepinephrine after tobacco smoking, intravenous nicotine infusion, and use of a nicotine nasal spray. SUBJECTS AND METHODS: Arterial and venous blood samples were drawn simultaneously from 12 male smokers. Six subjects received a single dose of 1 mg nicotine nasal spray, and six subjects smoked cigarettes, one puff per minute for 10 minutes. All 12 subjects were administered nicotine as a 30-minute infusion beginning 70 minutes after administration of the nicotine nasal spray or commencement of smoking. RESULTS: The mean peak arterial plasma concentrations of nicotine (Cmax) after smoking or administration of nicotine nasal spray, or intravenous nicotine averaged twofold those of venous plasma. For nicotine nasal spray, the time to Cmax was much faster for arterial than for venous plasma (median, 5 versus 18 minutes, p < 0.01). Intravenous nicotine produced the greatest increase in plasma epinephrine concentration, although smoking had a greater chronotropic effect. Acute tolerance to the chronotropic effects of nicotine was suggested at pharmacodynamic analysis with venous nicotine concentrations, whereas analysis of arterial concentrations found the opposite--a time lag between plasma concentration and effect. CONCLUSION: Nicotine is rapidly absorbed from nicotine nasal spray. The Cmax of nicotine after smoking or administration of nicotine nasal spray, or intravenous nicotine is substantially higher in arterial than venous plasma. Acute tolerance to the chronotropic effects of nicotine is not apparent if arterial plasma concentrations are measured.

Administration, Intranasal↗

PubMed2001

Noradrenaline in the bed nucleus of the stria terminalis is critical for stress-induced reactivation of morphine-conditioned place preference in rats.

The effect of noradrenaline in the bed nucleus of the stria terminalis and locus coeruleus on maintenance and reactivation of morphine-conditioned place preference induced by footshock stress was investigated in rats. After receiving alternate injection of morphine (10 mg/kg) and saline for 6 consecutive days, the rats spent more time in the drug-paired compartment (morphine-conditioned place preference) on day 7. These animals did not show morphine-conditioned place preference on day 37 following sham-footshock once every 3 days from days 8 to 36 (28 days drug-free). However, 15 min of intermittent footshock once every 3 days could induce the maintenance of morphine-conditioned place preference on day 37 with significantly more time spent in the drug-paired compartment than on day 0. Microinjection of the alpha(2)-adrenoceptor agonist, clonidine (0.1 or 1 microg), into the locus coeruleus 30 min before footshock did not affect stress-induced maintenance of conditioned place preference. However, infusions of clonidine (1 microg) into the bed nucleus of the stria terminalis significantly attenuated the maintenance of conditioned place preference induced by footshock stress. In another experiment, after a 21-day extinction of morphine-conditioned place preference, a single footshock could reactivate the morphine place preference that was significantly blocked by pretreatment with infusion of clonidine (0.1 or 1 microg) into the bed nucleus of the stria terminalis but not the locus coeruleus. Reactivation of morphine-conditioned place preference elicited by footshock stress was significantly inhibited by 6-hydroxydopamine-induced lesions in the ventral noradrenergic bundle, most of the norepinephrine input to the bed nucleus of the stria terminalis arising from caudal brain stem noradrenergic cell groups. In contrast, chemical lesions of the dorsal noradrenergic bundle that arises from the locus coeruleus had no such effects. These findings suggest that noradrenergic neurons in locus coeruleus are not involved in stress-induced reinstatement of drug-seeking and further clearly demonstrate that noradrenaline in the bed nucleus of the stria terminalis plays a critical role in mediating this effect. Comprehension of the neurochemical events underlying the stress-induced and the bed nucleus of the stria terminalis-mediated reinstatement of drug-seeking may, therefore, throw more light on the biological bases of drug dependence and addictive behavior

Adrenergic alpha-Agonists↗

PubMed2005

[Migraine with psychiatric co-morbidity].

Investigation of migraine co-morbidity has confirmed a strong association between depression, anxiety disorders (particularly panic and phobia) and migraine. However, research into the possible mechanisms underlying these associations remains limited. The literature also indicates that migrainers are at reduced risk of suffering from anxiety, mood disorders and substance-related disorders compared with medication overuse headache sufferers. Patients suffering from medication overuse headache sometimes exhibit addictive behavior for acute migraine drugs. Finally, migrainers show increased non-specific neurotic suffering.

Anxiety↗

PubMedDate not supplied

Iboga compounds reverse the behavioural disinhibiting and corticosterone effects of acute methamphetamine: Implications for their antiaddictive properties.

This study investigated the effects of pretreatment with the putative antiaddictive compound, ibogaine (IBO), and its synthetic derivative, 18-methoxycoronaridine (18-MC), on the changes in behaviour in an elevated plus maze and the changes in corticosterone (CORT) produced by a low dose of methamphetamine (METH). In the elevated plus maze, the acute administration of METH (0.1 mg/kg ip, -20 min) produced an increase in both the number and the duration of open arm entries relative to saline (SAL)-treated controls. No effect of METH administration was observed on the total number of arm entries. These data indicated that METH alone produced either anxiolysis or behavioural disinhibition in this paradigm. More consistent with the latter possibility, the open arm behaviour of METH controls was associated with an increase in plasma levels of CORT, supporting a facilitatory role for CORT in this METH-induced effect. Pretreatment with both IBO and 18-MC (40 mg/kg ip, 19 h earlier) antagonized the behavioural disinhibiting effects of acute METH without altering locomotor activity. In addition, both iboga agents antagonized the increase in CORT produced by METH. These data provide insight into yet another potential mechanism through which iboga compounds may exert their antiaddictive effects, a reversal of the behavioural disinhibiting properties of stimulant drugs. Furthermore, these data indicate that this reversal is related to effects of iboga compounds on the stimulation of neuroendocrine systems by stimulant drugs.

Animals↗

PubMed1998

The role of stress in drug self-administration.

Environmental experiences have an important effect on the sensitivity of an individual to drugs of abuse. Studies of drug self-administration in laboratory animals have shown that both physical and psychological stressors facilitate the acquisition of drug self-administration, probably by increasing the reinforcing efficacy of drugs of abuse. Stressors also facilitate the reinstatement of drug taking even after prolonged periods of withdrawal. The adrenal hormones, glucocorticoids, which increase the sensitivity of mesencephalic dopaminergic neurones to drugs, seem to be one of the biological substrates of the effects of stress on the propensity to develop drug intake. In this review, Pier Vincenzo Piazza and Michel Le Moal discuss theories of drug abuse, the influence of different stressful experiences on drug self-administration and their possible mechanisms of action.

Adrenal Cortex Hormones↗

PubMed2003

Selective induction of c-Fos immunoreactivity in the prelimbic cortex during reinstatement of heroin seeking induced by acute food deprivation in rats.

We previously reported that acute 1-day food deprivation reinstates heroin seeking in rats. The goal of the present study was to begin identifying brain sites potentially involved in this effect. For this purpose, we measured, by immunohistochemistry, the expression of c-Fos following a test for food deprivation-induced reinstatement. Groups of rats (n=9-10 per group) were trained to lever-press for heroin (0.05-0.1mg/kg/infusion) or saline for 10 days (9 h/day); each infusion was paired with a cue light. Rats were then given 10 days of extinction during which the heroin and saline syringes were removed. Next, a test for reinstatement was conducted after exposure to 0 (baseline) or 1-day food deprivation. During training, lever pressing for heroin increased over days, while responding for saline infusions paired with the cue light decreased over time. During extinction, responding on the heroin-paired lever decreased over time, while responding on the saline-paired lever remained low. In heroin-trained rats, food deprivation induced a large increase in responding on the lever associated with drug infusions. Surprisingly, food deprivation also modestly increased responding in the saline-trained rats. Food deprivation selectively increased c-Fos immunoreactivity (IR) in the prelimbic cortex of heroin-trained, but not saline-trained, rats (n=4 per condition). Food deprivation also increased c-Fos IR in both heroin- and saline-trained rats in the basolateral amygdala and the ventrolateral bed nucleus of stria terminalis (BNST), but had no effect on c-Fos expression in the dorsolateral BNST, cingulate cortex, nucleus accumbens, and central amygdala. These results raise the possibility that the prelimbic cortex is involved in food deprivation-induced reinstatement of heroin seeking.

Animals↗