Differential effects of centrally injected AVP on heart rate, core temperature, and behavior in rats.
After intracerebroventricular (icv) injection of arginine-vasopressin (AVP; 0.1, 1, 3, 10, 30 and 100 ng) or artificial cerebrospinal fluid (aCSF), heart rate (HR), core temperature (CT), and gross activity were monitored by a wireless telemetry system in rats in the home cage for a 60-min period. In addition, the simultaneous occurrence of various behaviors was recorded by an observer. Also, two structurally related peptides, oxytocin (OXT) and desglycinamide-arginine vasopressin (DGAVP), were tested (10 and 100 ng). Both the time-effect and dose-response relationships of AVP-induced changes in HR and CT were biphasic. Lower doses of AVP produced a tachycardia, whereas injection of higher doses of AVP caused a tachycardia preceded by a significant bradycardia. The concomitant mild rise in CT seen in rats treated with 1 and 3 ng AVP or with aCSF was attenuated in rats given 10 ng AVP; 30 ng AVP resulted in an immediate significant fall in CT, which was restored to control values at 30 min after administration. An inverted U-shaped dose-response relationship was observed for gross activity, locomotion, and rearing behavior, whereas grooming behavior was most marked after the highest dose of AVP. OXT induced a grooming response and cardiac acceleration at the 100-ng dose only, whereas DGAVP produced no effect. To investigate the role of endogenous AVP in the maintenance of tonic ANS activity under resting conditions, rats were treated intracerebroventricularly (icv) with the V1 antagonist d(CH2)5-[Tyr(Me)2]AVP or polyclonal antiserum (W1E) against AVP. During the first 10 min after icv injection of 3 and 10 ng of the antagonist, an increase in HR, CT, and behavioral activation was observed, effects opposite to those produced by the higher dose of AVP. The same variables remained unchanged after administration of 100 ng of the antagonist. W1E injected icv was without effect. In summary, central effects of AVP on autonomic and behavioral activity seem to be mediated by differential neural pathways. In addition, a structure-activity relation seems to exist for the AVP-induced effects. Finally, these results suggest that AVP plays but a minor role in the maintenance of tonic activity of the ANS.
Diamant
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Rudolf Magnus Institute, Department of Pharmacology, Medical Faculty, University of Utrecht, The Netherlands.
De Wied
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D000818:Animals; D000906:Antibodies / Q000502:physiology; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects*; D001921:Brain / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010121:Oxytocin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000276:immunology
D000906:Antibodies; D014667:Vasopressins; D001127:Arginine Vasopressin; C015119:argipressin, des-GlyNH2(9)-; D010121:Oxytocin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-