MITIGATION OF THE SOMNOLENCE OF INSULIN-INDUCED HYPOGLYCEMIA BY A VASOPRESSIN V-1 RECEPTOR ANTAGONIST IN THE RHESUS-MONKEY

Insulin-induced hypoglycemia causes somnolence in rhesus monkeys, a ph enomenon usually considered an aspecific consequence of neuroglycopeni a. Previous observations from our laboratory have raised the possibili ty that arginine vasopressin (AVP) may also play a role ill this decre ase in wakefulness. In the present study we tested this hypothesis by inducing hypoglycemia ( similar to 40 mg/dl) in ovariectomized rhesus monkeys by intravenous administration of insulin in the presence of co ntinuous intracerebroventricular infusions of the V-1 receptor antagon ist [deamino-Pen(1),O-Me-Tyr(2),Arg(8)]-vasopressin (180 mu g/60 mu l per h) or of its vehicle alone (artificial cerebrospinal fluid, 60 mu l/h). Wakefulness was assessed by a scoring system by observers blinde d to the experimental protocol. The AVP antagonist significantly atten uated the decrease in wakefulness observed in response to insulin-indu ced hypoglycemia (p < .03) without increasing blood glucose levels. Th ese and previous findings suggest that the somnolence induced by a mod erate degree of hypoglycemia may not entirely be the direct consequenc e of neuroglycopenia and that AVP may, directly or indirectly, be invo lved. (C) 1998 Elsevier Science Ltd. All rights reserved.