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

The effects of single and repeated administration of amphetamine (5 mg/kg, i.p., twice a day for 14 days) on the thyrotropin-releasing hormone (TRH) level, release and receptors in the rat striatum and nucleus accumbens were evaluated. Both treatments decreased the TRH level in those structures at 2 h after the drug injection. These effects were accompanied with elevation of the basal release of TRH from the nucleus accumbens and striatal slices at the same time point, whereas the stimulated (K+, 56 mM) TRH release was attenuated following repeated amphetamine administration. Acute amphetamine had no effect on the density and affinity of TRH receptors. Repeated amphetamine increased the B-max of TRH receptors in the striatum (by ca 49%) and nucleus accumbens (by ca 38%) at 2 h after the last drug injection. At 72 h after the last amphetamine administration, the B-max of the TRH receptor in the striatum was still elevated (by ca 42%), whereas in the nucleus accumbens it returned to control level. No changes in the affinity of TRH receptors following repeated amphetamine were found. The obtained results indicate that repeated amphetamine evokes long- and short-term up-regulation of TRH receptors in the rat striatum and nucleus accumbens, respectively. Furthermore, it is suggested that these changes may be an adaptive response to the amphetamine-induced alterations in the TRH tissue level and release.