Behaviour of pigs given corticotrophin-releasing hormone in combination with flumazenil or diazepam

The possible involvement of an endogenous benzodiazepine (BZ) inverse agonist in the activational effects of corticotrophin-releasing hormone (CRH) on behaviour was examined in pigs given porcine CRH (75 mug) intracerebroventricularly (i.c.v.) and the BZ antagonist flumazenil (FLU; 0.09 mg/kg) intravenously (i.v.). In Experiment 1, behaviour was recorded for 75 min in pigs (n = 5) given i.v. FLU or saline (SAL) followed by i.c.v. CRH or vehicle (VEH). Significant changes in arousal, posture and ore-nasal activity were induced by CRH, whereas FLU alone had no effect but appeared to reduce some responses to CRH. In Experiment 2, behaviour was observed for 60 min in pigs (n = 6) given i.c.v. CRH followed by i.v. FLU, VEH or diazepam (DZ; 0.2 mg/kg). Behavioural responses to CRH, however, were unaffected by FLU, whereas certain aspects of arousal, posture and ore-nasal activity were reduced by DZ; a higher dose of DZ (0.3 mg/kg) given before CRH tended to enhance these inhibitory effects. All treatments also produced similar increases in plasma cortisol. Taken together with previous findings, the negligible effect of FLU in this study suggests that endogenous ligands for the BZ binding site on the GABA(A) receptor are of little importance in regulating the behavioural actions of CRH in swine. (C) 2000 Elsevier Science Inc. All rights reserved.