Intra-VTA Baclofen Attenuates Cocaine Self-Administration on a Progressive Ratio Schedule of Reinforcement

doi:10.1016/S0091-3057(00)00286-0

Pharmacology Biochemistry and Behavior

Volume 66, Issue 4, August 2000, Pages 857-862

https://doi.org/10.1016/S0091-3057(00)00286-0 Get rights and content

Abstract

The effect of microinjections of baclofen into the ventral tegmental area (VTA), nucleus accumbens, or striatum on cocaine self-administration reinforced on a progressive ratio schedule was investigated. Intra-VTA baclofen produced the most potent modulation of cocaine intake, causing a significant reduction in cocaine-reinforced break points at a dose (56 ng/side) that was substantially lower than doses necessary to produce comparable reductions in the nucleus accumbens or striatum. During the time that cocaine-reinforced responding was suppressed, rats demonstrated the capacity to complete several hundred responses on a concurrently available food-reinforced lever, indicating that the effect of baclofen on cocaine intake was not due to a generalized disruption in operant responding. The results indicate that GABA_B receptors in the VTA may have the potential to modulate reward processes associated with cocaine use.

Section snippets

Subjects

Subjects were male Wistar rats (Charles River Farms, Quebec) weighing 275–300 g at the start of the experiment. All animals were placed under quarantine for 1 week following arrival at the facility and were maintained on a 12 L:12 D cycle (lights on at 1500 h). The care and treatment of all animals conformed with the standards of the Canadian Council on Animal Care and the guidelines promulgated by the Wake Forest University Animal Care and Use Committee and the National Institutes of Health.

Procedures and Apparatus

Results

The histological localizations of the bilateral injection cannulae in the different brain regions are shown in Fig. 1. A total of five animals were included in the VTA group, and the NAC and STR groups contained six animals each. In all regions studied, intracerebral injections of baclofen produced dose-dependent decreases in cocaine-reinforced break points.

Figure 2 (left) shows the effect of several doses of baclofen on responding under a PR schedule of reinforcement. Although baclofen

Discussion

The present results demonstrate that intracerebral injections of the GABA_B agonist baclofen into the VTA, NAC, or STR reduce cocaine self-administration under a PR schedule of reinforcement. Microinjections of baclofen into the VTA produced the most potent modulation of cocaine self-administration, decreasing cocaine-reinforced break points at doses that were three times lower than those required to produce comparable reductions from injections into the NAC or STR. Several other studies have

Acknowledgements

This reserach was funded by the Medical Research Council of Canada and National Institute on Drug Abuse, P50DA06634.

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ArticlesIntra-VTA Baclofen Attenuates Cocaine Self-Administration on a Progressive Ratio Schedule of Reinforcement

Abstract

Section snippets

Subjects

Procedures and Apparatus

Results

Discussion

Acknowledgements

Neuropharmacology

Brain Res.

Life Sci.

Brain Res. Rev.

Brain Res.

Behav Brain Res.

J. Neurosci. Methods

Neuropsychopharmacology

Eur. J. Pharmacol.

Brain Res.

Behav. Brain Res.

Brain Res.

Neuropharmacological mechanisms of drug rewardBeyond dopamine in the nucleus accumbens

Crit. Rev. Neurobiol.

Effect of baclofen on cocaine self administration reinforced under FR1 and progressive ratio schedules

Psychopharmacology (Berlin)

Effects of baclofen on maintenance and reinstatement of intravenous cocaine self-administration in rats

Psychopharmacology (Berlin)

A concurrently available nondrug reinforcer prevents the acquisition or decreases the maintenance of cocaine-reinforcement

Psychopharmacology (Berlin)

Autoradiographic localization of gamma aminobutyric acidA receptors within the ventral tegmental area

Neurochem. Res.

Food deprivation affects extinction and reinstatement of responding in rats

Psychopharmacology (Berlin)

Food deprivation and acquisition of intravenous cocaine self-administration in ratsEffect of naltrexone and haloperidol

J. Pharmacol. Exp. Ther.

GABAergic attenuation of cocaine-induced dopamine release and locomotor activity

Synapse

Articles
Intra-VTA Baclofen Attenuates Cocaine Self-Administration on a Progressive Ratio Schedule of Reinforcement

Autoradiographic localization of gamma aminobutyric acid_A receptors within the ventral tegmental area