Contribution of Ventral Tegmental GABA Receptors to Cocaine Self-administration in Rats

• Published in: Neurochemical research Vol. 33; no. 3; pp. 459 - 467
• Main Authors: Backes, E. N., Hemby, S. E.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.03.2008; Springer Nature B.V
• Subjects: Animals; Baclofen - analogs & derivatives; Baclofen - pharmacology; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cocaine-Related Disorders - metabolism; Cocaine-Related Disorders - psychology; Conditioning, Operant - drug effects; Dose-Response Relationship, Drug; Food; GABA Agonists - pharmacology; GABA Antagonists - pharmacology; Immunohistochemistry; Male; Muscimol - pharmacology; Neurochemistry; Neurology; Neurosciences; Original Paper; Picrotoxin - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, GABA - physiology; Receptors, GABA-A - drug effects; Reinforcement (Psychology); Self Administration; Ventral Tegmental Area - metabolism; Ventral Tegmental Area - pathology; Ventral Tegmental Area - physiology; GABA; Reinforcement; Cocaine; Rat; Ventral tegmental area
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-007-9454-2

Recent evidence has suggested that compounds affecting GABAergic transmission may provide useful pharmacological tools for the treatment of cocaine addiction. Using a rat model of self-administration, the present study examined the effects of GABA agonists and antagonists injected directly into the ventral tegmental area (VTA) on cocaine intake in rats trained to self-administer cocaine (0, 125, 250 and 500 μg/infusion) under an FR5 schedule of reinforcement. Separate groups of rats received bilateral intra-VTA injections of the GABA-A antagonist picrotoxin (34 ng/side, n  = 7; 68 ng/side, n  = 8), GABA-A agonist muscimol (14 ng/side, n  = 8), GABA-B agonist baclofen (56 ng/side, n  = 7; 100 ng/side, n  = 6), picrotoxin (68 ng/side) co-injected with the GABA-B antagonist 2-hydroxysaclofen (100 ng/side, n  = 7; 2 μg/side, n  = 8) or artificial cerebrospinal fluid (aCSF, n  = 6) to assess the effects of the various compounds on the cocaine self-administration dose-response curve. Both picrotoxin and baclofen reduced responding maintained by cocaine, whereas muscimol had no effect on responding. In contrast, neither picrotoxin ( n  = 6) nor baclofen ( n  = 8) affected responding maintained by food. Interestingly, 2-hydroxysaclofen effectively blocked the suppression of responding produced by picrotoxin, suggesting that both picrotoxin and baclofen exert their effects via activation of GABA-B receptors. Additionally, these effects appear to be specific to cocaine reinforcement, supporting current investigation of baclofen as a treatment for cocaine addiction.