Cocaine self-administration alters the locomotor response to microinjection of bicuculline into the ventral tegmental area of rats.
Several studies indicate that repeated administration of cocaine can alter GABA(A) receptor function, particularly in the mesolimbic pathway. The purpose of the present study was to assess the effect of cocaine self-administration on GABA(A) receptor activity in the ventral tegmental area (VTA), measured by bicuculline-induced rotational behavior. In order to test whether the hypothesized alteration in GABA(A) receptor function persisted during withdrawal, rats were tested when drug-nai;ve and at two time points after cocaine self-administration. Eighteen rats were implanted with intrajugular catheters and unilateral guide shafts aimed at the VTA. Microinjection of the GABA(A) receptor antagonist bicuculline (10, 25 and 50 ng) produced a dose-dependent turning behavior in a direction ipsilateral to the side of the injection. A subset of six rats was given up to 2 weeks exposure to intravenous cocaine by self-administration and was tested for bicuculline-induced rotations early in withdrawal (24 h) and again at a late withdrawal time point (between 11 and 14 days after the last cocaine session). Cocaine self-administration reduced sensitivity to bicuculline-induced rotations at the early but not at the late withdrawal point, when compared to sensitivity in drug-naive animals. A separate control study that was conducted in seven rats determined that repeated injections of bicuculline in the cocaine self-administration animals was not the cause of the decrease in behavioral response to bicuculline at the early withdrawal time point. These results suggest that exposure to cocaine via self-administration reduces the function of GABA(A) receptors in the ventral midbrain, but this reduction in receptor sensitivity did not persist beyond 10 days of withdrawal from cocaine.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D004361:Drug Tolerance; D018756:GABA Antagonists / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D017557:Ventral Tegmental Area / Q000187:drug effects*
D018765:Dopamine Uptake Inhibitors; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D003042:Cocaine; D001640:Bicuculline