RT Journal Article SR Electronic T1 Ethanol-induced locomotor stimulation in rats after thyrotropin-releasing hormone. JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 731 OP 737 VO 229 IS 3 A1 G R Breese A1 S Coyle A1 A C Towle A1 R A Mueller A1 T J McCown A1 G D Frye YR 1984 UL http://jpet.aspetjournals.org/content/229/3/731.abstract AB Ethanol-induced sedation in Sprague-Dawley rats was antagonized by intracisternally administered thyrotropin releasing hormone (TRH) at a dose as low as 1 microgram. Furthermore, when a dose of 25 micrograms or greater of TRH was combined with ethanol doses above 2 g/kg, the locomotor activity was significantly greater than observed for TRH alone. A dose-related increase in activity was observed when varying doses of ethanol were administered with a constant dose of TRH (100 micrograms). This increase in locomotion induced by the TRH-ethanol combination could not be attributed to a change in TRH concentration, ethanol distribution or to a pituitary action of TRH. Inasmuch as tert-butanol in combination with TRH produced the same effects as ethanol, the hyperactivity does not appear to be associated with acetaldehyde formation. TRH acid and His-Pro-diketopiperazine, metabolites of TRH, did not produce hyperactivity when administered with ethanol, whereas MK-771, a TRH analog, produced a significant increase in locomotion in ethanol-treated rats greater than that for MK-771 alone. Three lines of evidence suggested that the hyperactivity induced by the TRH-ethanol combination could not be attributed to an influence of ethanol on the stimulant effects of TRH. First, pentobarbital- and chlordiazepoxide-induced depression of locomotion was antagonized by TRH (100 micrograms) but, unlike ethanol, locomotor stimulation greater than that for TRH was not observed. Second, behavioral observations did not reveal ethanol altering any effects of TRH that would compete with locomotion.(ABSTRACT TRUNCATED AT 250 WORDS)