EFFECTS OF REPEATED COCAINE ADMINISTRATION ON THE THYROTROPIN-RELEASING-HORMONE LEVEL AND RECEPTORS IN THE RAT-BRAIN

The effects of single and repeated administration of cocaine on the th yrotropin-releasing hormone (TRH) level and receptors in discrete rat brain structures were evaluated. Male Wistar rats received saline or c ocaine (15 mg/kg i.p., once an hour within 3 h, for 8 days). The anima ls were killed by decapitation at 45 min and 72 h (chronic group only) after the last injection. A radioimmunoassay (RIA) study showed that a single dose of cocaine increased the TRH level in the striatum by 68 %, but had no significant effect on the peptide content in the nucleus accumbens, hippocampus, amygdala, septum, hypothalamus, frontal and p refrontal cortex at 45 min after the drug injection. Repeated administ ration of cocaine increased the TRH level in the striatum by 89% at 45 min, and in the hippocampus by 26% at 72 h after the last dose. No ch anges in the TRH level were found in other brain structures. In vitro cocaine (10(-6)-10(-4) M) inhibited the K+-stimulated release in a con centration-dependent manner, but had no effect on the basal release of TRH from the striatum and nucleus accumbens of naive rats. Acute coca ine decreased the B-max of TRH receptors in the striatum, but had no e ffect on the density and affinity of TRH receptors in other brain regi ons. Repeated administration of cocaine evoked a long-lasting decrease in the B of TRH receptors in the striatum (by c. 30%), whereas an inc rease in that parameter was observed in the frontal cortex. The B-max and affinity of TRH receptors following repeated cocaine remained unch anged in the nucleus accumbens. The results obtained indicate that coc aine affects the TRH system mainly in the striatum, and to a lesser ex tent in the nucleus accumbens, cortex and hippocampus. Furthermore, th e above changes do not resemble those induced by amphetamine, which po ints to certain differences in adaptation of the TRH neuronal system t o these psychostimulants. On the other hand, the increase in the hippo campal TRH level during both chronic cocaine and morphine withdrawal i s a common feature of the mechanism of dependence on these drugs.