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 hormo ne (TRH) level, release and receptors in the rat striatum and nucleus accumbens were evaluated. Both treatments decreased the TRH level in t hose structures at 2 h after the drug injection. These effects were ac companied with elevation of the basal release of TRH from the nucleus accumbens and striatal slices at the same time point, whereas the stim ulated (K+, 56 mM) TRH release was attenuated following repeated amphe tamine administration. Acute amphetamine had no effect on the density and affinity of TRH receptors. Repeated amphetamine increased the B-ma x 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 las t amphetamine administration, the B-max of the TRH receptor in the str iatum was still elevated (by ca 42%), whereas in the nucleus accumbens it returned to control level. No changes in the affinity of TRH recep tors following repeated amphetamine were found. The obtained results i ndicate that repeated amphetamine evokes long- and short-term up-regul ation of TRH receptors in the rat striatum and nucleus accumbens, resp ectively. Furthermore, it is suggested that these changes may be an ad aptive response to the amphetamine-induced alterations in the TRH tiss ue level and release.