Alterations in gamma-aminobutyric acid(B) receptor binding in the rat brain after reinstatement of cocaine-seeking behavior.

We examined neuroadaptive changes in GABA(B) receptor binding following reinstatement of cocaine-seeking behavior in rat brain structures using a "yoked" procedure and quantitative autoradiographic analysis. To estimate the distribution of GABA(B) receptors in several brain areas, we used [(3)H]CGP 54626, a GABA(B) receptor antagonist. The binding of [(3)H]CGP 54626 in the nucleus accumbens and the amygdaloid complex was decreased by about 20% in rats that actively administered cocaine. Similar decreases were seen in the animals that were passively administered cocaine; these rats also demonstrated decreased GABA(B) receptor binding in the prefrontal and frontal cortices, septum and dorsal striatum. The binding of [(3)H]CGP 54626 in several rat brain areas was decreased during 10-day withdrawal from self-administered cocaine. The cocaine-priming dose (10 mg/kg, ip) induced a significant increase of [(3)H]CGP 54626 binding in the core of the nucleus accumbens, substantia nigra (reticular part), prefrontal and frontal cortices and septum in rats withdrawn from cocaine self-administration. The presentation of the conditioned stimulus (tone + light) associated with previous cocaine self-administration induced a significant decrease of [(3)H]CGP 54626 binding in the mediodorsal thalamic nucleus and amygdaloid complex in the rats withdrawn from cocaine self-administration. Increases in GABA(B) receptor binding in limbic regions during cocaine-induced reinstatement likely reflect motivational states that were present during active drug self-administration.