The effects of thyrotropin-releasing hormone, metabolites and analogues on locomotor activity in rats.

Thyrotropin-releasing hormone (TRH) has generally been reported to increase locomotor activity in rats; however there are also some negative reports. In order to identify the possible causes for this discrepancy, the effects of intra-cerebroventricular injection of TRH, its metabolites 'acid TRH' (TRH-OH) and His-Pro-diketopiperazine (DKP), and two analogues 3-methyl-His-TRH and RX 77368 (3,3-dimethyl-Pro-TRH), were assessed using photocell activity cages. All compounds were tested in groups of eight rats in the afternoon (1300-1700 h), but in addition TRH and DKP were tested in two further groups of rats during the morning (0900-1230 h). TRH and DKP failed to induce a significant rise in activity during the morning test period, but TRH did have a significant effect when tested in the afternoon. Both TRH and TRH-OH caused dose dependent increases in locomotor activity, whereas DKP and the two analogues had no effect. This stimulation of activity was shown to be at least partly mediated by dopamine since locomotor enhancement was blocked in a second experiment using the dopamine antagonist alpha-Flupenthixol. The results are discussed in terms of actions on the mesolimbic dopamine system, and the importance of circadian variations within this system to the expression of peptide effects in general.