Effects of a new TRH analogue, YM-14673, on spontaneous motor activity in rats.

The effects of a new TRH analogue, YM-14673 (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide dihydrate) on spontaneous motor activity (SMA) were compared with those of TRH in rats. Intraperitoneal, oral and intracerebral administrations of YM-14673 caused a significant and dose-dependent increase in SMA. TRH also showed similar actions as YM-14673 did, except after oral dosing. These actions of YM-14673 were about 20-100 times more potent than those of TRH. Pretreatment with haloperidol, alpha-methyl-p-tyrosine (alpha-MT) and amino-oxyacetic acid (AOAA) but not atropine, inhibited the ability of both YM-14673 and TRH to increase SMA. Focal microinjection into the nucleus accumbens of both YM-14673 and TRH induced about 100 times more potent increases in SMA than similar injections into the dorsal striatum. It is suggested that YM-14673 possesses more potent facilitatory effects on SMA than TRH, and that these appear to be mediated mainly by the mesolimbic dopaminergic system rather than by the nigrostriatal one. Other possible mechanisms are also discussed.