Neuroadaptive changes in the rat brain GABA(B) receptors after withdrawal from cocaine self-administration.

We examined neuroadaptive changes in gamma-aminobutyric acid (GABA)(B) receptor binding following cocaine self-administration and its withdrawal in several rat brain structures using a "yoked" procedure and a quantitative autoradiographic analysis. In order to estimate the distribution of GABA(B) receptors in several brain areas, we used ([S-(R,R)]-[3-[[1-(3,4-diclorophenyl)ethyl]amino]-2-hydroxypropyl]([3,4-(3)H]-cyclohexylmethyl) phosphinic acid) ([(3)H]CGP 54626), a GABA(B) receptor antagonist. The binding of [(3)H]CGP 54626 in the nucleus accumbens subareas and the amygdala was decreased by ca. 20% in rats that actively self-administered cocaine. Similar decreases in the nucleus accumbens were seen in the animals passively receiving cocaine. These animals also showed a reduction in GABA(B) receptor binding in the prefrontal and frontal cortices, septum and dorsal striatum. The [(3)H]CGP 54626 binding in several rat brain areas was decreased after 10-day withdrawal from self-administered cocaine. In summary, the decreases in the GABA(B) receptor binding seem to reflect the effects of chronic administration of cocaine per se and not the motivated process of reinforced responding. Furthermore, withdrawal from cocaine self-administration evoked changes in the GABA(B) receptor binding in several rat brain areas that may indicate neurobiological adaptations.