The effects of thyrotropin releasing hormone on rats with lesions of the mesolimbic and nigrostriatal dopamine systems.

We report the effects of intracerebroventricular (ICV) administration of thyrotropin releasing hormone (TRH), a TRH metabolite histidyl-proline diketopiperazine (DKP) and systemically administered d-amphetamine (AMP) on the locomotor activity of two groups of rats which had previously received bilateral injections of either 6-hydroxydopamine (6-OHDA) or saline into the nucleus accumbens. Both TRH and AMP enhanced locomotor activity in control, but not lesioned animals, whereas DKP had very little effect. In a second experiment, the effects of ICV administration of saline, TRH and DKP were tested on rotational behaviour in rats with unilateral lesions of the substantia nigra. Neither peptide induced significant circling on its own. However, coadministration of TRH or DKP with systemically administered AMP enhanced rotation above that found after injection of AMP alone. These results suggest that TRH can act on mesolimbic and nigrostriatal dopamine systems, either directly or by modulating the effects of other dopaminergic agents.