Androgen-dependent vasopressinergic neurotransmission attenuates interleukin-1-induced sickness behavior

Abstract

Castrated male rats were found to be more sensitive than intact male rats to the depressing effects of recombinant human interleukin-1 beta (Il-1) on social exploration. This was the case whether Il-1 was injected acutely (1-5 micrograms/rat, i.p.) or continuously, via an implanted osmotic mini-pump (2 micrograms Il-1 per day). In this latter case, tolerance developed more rapidly to the behavioral effects of Il-1 than to its effects on body weight. Since there is evidence that extrahypothalamic arginine vasopressin (AVP) acts as an endogenous antipyretic in the brain and the local concentration of AVP is dependent on circulating androgens, we tested the hypothesis that the enhanced sensitivity of male rats to the behavioral effects of Il-1 was caused by a reduced brain concentration of vasopressin. Central injection of AVP (2.5 ng, i.c.v.) attenuated the behavioral effects of Il-1 (5 ng, i.c.v.) and this effect was more marked in castrated than in intact male rats. Conversely, central injection of an antagonist of the vasopressor receptors of AVP, dPTyr(Me)AVP (15 ng, i.c.v.) potentiated the behavioral effects of Il-1 (1 ng, i.c.v.) in intact but not in castrated male rats. These results are consistent with the possibility that androgen-dependent vasopressinergic neurons oppose the neural effects of Il-1.