The effect of neurotensin, TRH and the delta-opioid receptor antagonist ICI 174864 on alcohol-induced narcosis in rats.

The effects of microinjections of thyrotropin-releasing hormone (TRH), neurotensin and ICI 174864 into the nucleus accumbens, nucleus caudatus, septum and mesencephalic periaqueductal grey were studied on ethanol-induced narcosis in the rat. Levels of narcosis were assessed by alterations in ethanol-induced hypothermia and sleep time. Ethanol produces a 2 degree C fall in body temperature over the first hour which then recovered over the next 2 h. Sedation was produced to the extent that the righting reflex was lost for between 80 and 90 min. In the nucleus caudatus all 3 peptides were ineffective at altering narcosis. In the periaqueductal grey, septum and accumbens, TRH (5 micrograms) and ICI 174864 (1 microgram) microinjections significantly reduced the sleep time by between 50 and 70%. ICI 174864 was approximately 10 times more potent that TRH at reducing the sleep time. In addition, both these peptides significantly accelerated the recovery from the ethanol-induced hypothermia in the periaqueductal grey, septum and accumbens. ICI 174864 prevented the ethanol-induced fall in body temperature. Neurotensin (5 micrograms) significantly increased the sleep time by up to 50% and potentiated the ethanol-induced hypothermia. These results suggest that the administration of TRH or the blockade of delta-opioid receptors, resulting in an inhibition of endogenous enkephalin transmission, may significantly inhibit ethanol narcosis in the rat. Opposing this, the application of neurotensin appears to potentiate ethanol narcosis. These results also indicate that endogenous enkephalin release plays an important role in ethanol narcosis.