Further studies on the pharmacological effects of pentobarbitone and 2.4-dinitrophenol injected into the cerebral ventricles of the mouse and rat

Abstract

N.S. DOGGETT and P.S.J. SPENCER, Further studies on the pharmacological effects of pentobarbitone and 2.4-dinitrophenol injected into the cerebral ventricles of the mouse and rat, Europcan J. Pharmacol. 22 (1973) 150–155. A comparison of some pharmacological effects of pentobarbitonc and 2,4-dinitrophenol (DNP) was made after intracerebroventricular (i.c.v.) injection in the conscious mouse and rat. Both compounds produced marked hypothermia after injection by this route. They differed, however, in that sub-hypnotic doses of DNP reduced conditioned avoidance responses (C.A.R.) with no effect on unconditioned responses (U.R.) in trained rats, whereas sub-hypnotic doses of pentobarbitone reduced both C.A.R. and U.R. Determinations of whole-brain amine levels showed that pentobarbitone increased dopamine with no effect on noradrenaline, whereas DNP had no effect on dopaminc but reduced noradrenalinc. 5-Hydroxytryptamine levels were reduced by both compounds. Finally, it was demonstrated that i.c.v. DNP potentiates the hypnotic activity of peripherally-administered pentobarbitone. Although both compounds may share a common mechanism in the production of hypothermia, the present experiments provide further evidence of dissimilarities in the mechanisms involved in the production of their central depressant activity.