1,720,972 research outputs found
Gamma-hydroxybutyric acid: an evaluation of its rewarding properties in rats and mice
No full textGamma-hydroxybutyric acid, an endogenous compound present in mammalian brain and supposed to be a neurotransmitter or neuromodulator, has been shown to affect several aspects of dependence from some drugs of abuse. It has been successfully used in clinical practice to alleviate both alcohol and opiate withdrawal symptoms. The aim of this study was to investigate whether gamma-hydroxybutyric acid possesses rc warding properties by means of conditioned place preference and intravenous self-administration paradigms. In the present study, gamma-hydroxybutyric acid induced conditioned place preference in rats, was intravenously self-administered by drug naive mice, and altered cocaine intravenous self-administration in rats. Although to date the physiological role of this compound still re mains unclear, there is no doubt that gamma-hydroxybutyric acid, in addition to its proved effect on alcohol and opiate dependence, possesses reinforcing properties of its own and may interfere with the neurochemical events in the rewarding effects produced by psychostimulant drugs. Our investigation points out the abuse: liability of this drug, suggesting the use of particular precaution in handling gamma-hydroxybutyric acid as a clinically useful drug. (C) 2000 Elsevier Science Inc. All rights: reserved
Self-administration of the cannabinoid receptor agonist WIN 55,212-2 in drug-naive mice
No full textMarijuana is one of the most widely used illicit recreational drugs, However, contrary to the majority of drugs abused by humans, there is a general opinion that rewarding effects are not manifested by animals. We studied a synthetic cannabinoid agonist WIN 55,212-2 using an intravenous self-administration model in drug-naive mice. The results of this study show that WIN 55,212-2 was intravenously self-administered by mice in a concentration-dependent manner according to a bell-shaped curve. Thus, self-administration of WIN 55,212-2 significantly increased, with respect to the vehicle self-administration control group, at concentrations of 0.5 and 0.1 mg/kg per injection. However, at WIN 55,212-2 concentration of 0.5 mg/kg per injection, self-administration significantly decreased, The results obtained show how WIN 55,212-2 is able to elicit both rewarding and aversive effects depending on the concentration used. Pretreatment of mice with the cannabinoid CB1 receptor antagonist SR 141716A (0.25 mg/kg, i.p.) completely prevented WIN 55,212-2 (0.1 mg/kg per injection) self-administration, indicating that WIN 55,212-2 rewarding effects are specifically mediated by cannabinoid CB1 receptors, (C) 1998 LBRO, Published by Elsevier Science Ltd
Baclofen antagonizes intravenous self-administration of nicotine in mice and rats
No full textAims: gamma-Aminobutyric acid (GABA)-ergic transmission plays an important role in modulating reinforcing effects of different drugs of misuse. In particular, stimulation of GABA(B) receptors negatively influences self-administration of cocaine, heroin, nicotine, alcohol and gamma-hydroxybutyric acid. The effect and specificity of the GABA(B) agonist baclofen on nicotine misuse were studied on two animal models of self-administration. Methods: The effects of RS baclofen and the two isomers R baclofen and S baclofen were studied on the acute nicotine self-administration in drug-naive mice. The effect of RS baclofen was also studied in rats trained to chronically self-administer nicotine under a continuous reinforcement (FR1) schedule. Results: RS baclofen antagonizes nicotine intravenous self-administration at doses of 1.25-2.5 mg/kg intraperitoneally (i.p.). Furthermore, this effect is sterospecific. R baclofen completely prevented nicotine self-administration at the dose of 0.625 mg/kg i.p., whereas S baclofen was inactive up to the dose of 2.5 mg/kg i.p. In rats trained to self-administer nicotine, pretreatment with RS baclofen at the dose of 2.5 mg/kg i.p. significantly increased the rate of responding for nicotine. This effect was similar to the effect obtained when rats were pretreated with the nicotine central receptor antagonist mecamylamine (1 mg/kg i.p.). Conclusions: These data show that baclofen is able to antagonize nicotine-rewarding effects in mice and rats and suggest its potential clinical utility for the treatment of nicotine misuse
Rewarding properties of gamma-hydroxybutyric acid: an evaluation trouth place preference paradigm
No full textGamma-hydroxybutyric acid (GHB), a putative neurotransmitter or neuromodulator found in the mammalian brain, has been successfully used in clinical practice to alleviate both alcohol and opiate withdrawal symptoms. In the present study we used a conditioned place preference (CPP) paradigm to investigate whether GHB possesses rewarding properties in rats. In order to exclude possible artifacts due to experimental design, we evaluated the possibility of a shift in preference when rats are conditioned either on their non-preferred side or on a randomly assigned side of conditioning. In both experiments GHB was seen to induce CPP. Although to date the physiological role of this compound still remains unclear, there is no doubt that GHB, further to its proven effect on alcohol and opiates, possesses rewarding properties of its own. The abuse liability afforded by this drug suggests the use of particular caution in handling GHB as a clinically useful drug
CB1 cannabinoid receptor agonist WIN 55,212-2 decreases intravenous cocaine self-administration in rats
No full textThe effect of the CB, cannabinoid receptor agonist WIN 55, 212-2 on intravenous cocaine self-administration (IVSA) in rats was evaluated. Male Long Evans rats were implanted with silastic catheters through the external jugular vein. The IVSA was conducted in 3-h daily sessions with a fixed ratio (FR1) schedule: the experimental apparatus had a nose-poking response-like operandum. Intravenous pre-treatment with WIN 55, 212-2 (0.25, 0.5 and 1 mg/kg) to rats self-administering cocaine (0.25 or 0.5 mg/kg/inj) at stable baseline, reduces cocaine intake in a dose-dependent manner. The CB, receptor antagonist SR 141716A (3 mg/kg i.p.) completely reversed the WIN 55, 212-2-induced decrease of cocaine intake. However, pre-treatment of SR 141716A alone (up to dose of 9 mg/kg i.p.) was unable to modify cocaine IVSA. These results indicate that stimulation of CB, cannabinoid receptors activates rewarding mechanisms which produce reinforcing effects additional to those induced by cocaine. (C) 1999 Elsevier Science B.V. All rights reserved
Intravenous self-administration of gamma-hydroxybutyric acid in drug-naive mice
No full textThe reinforcing effects of gamma-hydroxybutyric acid (GHB) were studied by means of intravenous self-administration in drug-naive mice. GHB self-administration was concentration-dependent (0.01-0.5 mg/kg/inj) according to a bell-shaped curve. Pretreatment with the specific GHB receptor antagonist NCS-382 at a dose of 12.5 mg/kg i.p. completely antagonized the reinforcing effects of GHB. These data suggest that GHB is able to induce reinforcing effects in mice and support the hypothesis of an abuse liability of this drug. (C) 1998 Elsevier Science B.V./ECNP. All rights reserved
Baclofen antagonizes intravenous self-administration of gamma-hydroxybutyric acid in mice
No full textGamma -Hydroxybutyric acid (GHB) is a widely used recreational drug known to exert positive reinforcing effects in animals and humans. The GABAB receptor agonist baclofen has been proved to possess antimotivational effect and to inhibit alcohol, cocaine, heroin and nicotine intake. In the present study we evaluated the effect of baclofen on i.v, self-administration of GHB in drug-naive mice under a fixed-ratio (FR-I) schedule of reinforcement and nose-poking-like response as operandum. Results show that baclofen was able to completely prevent GHB seeking behaviour, decreasing the rate of responding to basal values, without showing any reinforcing properties when made contingent on nose-poking response. Our findings demonstrate that baclofen antagonises GHB i.v. self-administration, supporting an important role for the GABAB receptor in reward-related mechanisms underlying addictive behaviour. NeuroReport 12:2243-2246 (C) 2001 Lippincott Williams & Wilkins
Intravenous self-administration of the cannabinoid CB1 receptor agonist WIN 55,212-2 in rats
No full textRationale: Delta (9)-Tetrahydrocannabinol (Delta (9)-THC), the main psychoactive ingredient of marijuana, as well as synthetic cannabinoid (CB 1) receptor agonists, has led to negative or equivocal results when tested with the intravenous self-administration procedure, the best validated behavioural model for evaluating abuse liability of drugs in experimental animals. We recently reported, however, that the synthetic CB 1 receptor agonist WIN 55,212-2 is intravenously self-administered by drug-naive mice and that its self-administration is blocked by the cannabinoid CB 1 receptor antagonist SR 141716A. Objective: To assess a reliable model of cannabinoid intravenous self-administration in rats. Long Evans male rats were allowed the opportunity to self-administer WIN 55,212-2 at doses ranging from 6.25 to 50 mug/kg per injection, under a fixed-ratio 1 (FR1) schedule of reinforcement and nose-pokes as the operant responses. The effect of either a change in the unit drug dose available or a pretreatment with the specific CB I receptor antagonist SR 141716A were then investigated (maintenance phase). Finally, the extinction of the self-administration behaviour was evaluated. Results: Response rate depended on the drug dose available, with maximum rates occurring at 12.5 mug/kg per injection. Response rate increased following pretreatment with the specific CB I receptor antagonist, SR 141716A. Moreover, operant behaviour rapidly extinguished following both the substitution of saline or vehicle for cannabinoid and the disconnection of the drug delivery pumps. Conclusion: Rats will intravenously self-administer the synthetic CB I receptor agonist WIN 55,212-2 under specific experimental conditions, thus allowing further investigation of the neurobiological mechanisms underlying cannabinoid-taking behaviour
Cannabinoid CB1 antagonist SR 141716A attenuates reinstatement of heroin self-administration in heroin abstinent rats
No full textRats with a previous history of heroin self-administration were studied to assess interactions occurring between cannabinoids and opioids in an animal model of reinstatement of heroin-seeking behaviour. Rats were trained to self-administer heroin and after a long-term extinction were primed with one of the following non-contingent non-reinforced drug administrations: saline (or vehicle), heroin, synthetic cannabinoid CB1 receptor agonists (WIN 55,212-2 or CP 55,940), opioid antagonist (naloxone) or CB1 antagonist (SR 141716A), alone or in combination. After primings, lever-pressing activity was recorded and compared to those observed during previous phases of training and extinction. Results of this study showed that (i) priming injections of heroin (0.1 mg/kg) as well as CB1 agonists WIN 55,212-2 (0.15 or 0.30 mg/kg) and CP 55,940 (0.05 or 0.1 mg/kg) completely restore heroin-seeking behaviour; (ii) primings of naloxone (1 mg/kg) and SR 141716A (0.3 mg/kg) had no effect when administered alone; (iii) heroin-induced reinstatement was fully prevented by pre-treatment with either naloxone or SR 141716A; (iv) pre-treatment with SR 141716A significantly reduced WIN 55,212-2 and CP 55,940 priming effects. These results suggest that cannabinoid CB1 receptors play an important role in the mechanisms underlying relapse to heroin-seeking and depict CB1 antagonists as possible therapeutic agents for use in the prevention of relapse to heroin abuse. (c) 2005 Elsevier Ltd. All rights reserved
An endocannabinoid mechanism in relapse to drug seeking: A review of animal studies and clinical perspectives
No full textDetoxification from drug abuse is strongly threatened by the occurrence of renewed episodes of drug intake. In human addicts, relapse to drug seeking may take place even after a considerably long period from the last drug consumption. Over the last decade, the endocannabinoid system has received remarkable attention due to its unique features, including its rewarding properties closely resembling those of the most commonly abused substances and its multiple therapeutic implications. Although limited at present, evidence is now emerging on a possible participation of the endogenous cannabinoid system in the regulation of relapsing phenomena. Both stimulation and blockade of the central cannabinoid CB-sub1 receptor have proved to play an important role in drug- as well as in cue-induced reinstatement of drug seeking behavior. Indeed, while CB-sub1 receptor stimulation may elicit relapse not only to cannabinoid seeking but also to cocaine, heroin, alcohol and methamphetamine, this effect is significantly attenuated, when not fully prevented, by pretreatment with the CB-sub1 receptor antagonist rimonabant. However, corroborating data on the involvement of the cannabinoid system in stress-induced reinstatement are still rather scarce. The present review attempts to collect data obtained from different laboratories using diverse experimental approaches, to provide a comprehensive picture of the recent evidence of a relationship between the cannabinoid system and the neurobiological mechanisms leading to relapse. For each class of abused drugs, the conspicuous progress made in delineating the role of the endocannabinoid system in relapse to drug seeking has been examined by placing particular emphasis on the findings obtained from behavioral studies. After summarizing findings and implications emerging from the reviewed studies, we conclude by briefly discussing what information is still missing and how missing information might be obtained
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