ANXIOGENIC ACTIVITY OF INTRAVENTRICULARLY ADMINISTERED ARGININE-VASOPRESSIN IN THE RAT

Arginine-vasopressin (AVP), a mammalian neuropeptide, has been postula ted to function as a neurotransmitter or neuromodulator. There is clin ical evidence that, apart from its role in affective illness, AVP may be involved in anxiety syndromes as well. The present study investigat ed the putative anxiogenic effect of intracerebroventricularly (i.c.v. ) AVP administered in rats, using well validated animal models of anxi ety, including the open-field, elevated plus-maze, social interaction and feeding latency in a novel environment tests. Pentylenetetrazol (P TZ, 20 mg/kg, i.p.) was used as the standard anxiogenic agent for comp arison. In addition, the effect of AVP was assessed on rat brain tribu lin activity in terms of endogenous monoamine oxidase (MAO) A and B in hibition. Tribulin has been shown to be an endocoid marker of anxiety and stress. AVP (100, 200 and 500 ng/rat, i.c.v.) produced a dose-rela ted decrease in ambulation and rears, and an increase in immobility an d defaecation, in the open-field test. These doses of AVP produced a d ose-related decrease in the number of entries and time spent on the op en arms of the elevated plus-maze, reduced social interaction in paire d rats and increased the latency to feed in an unfamiliar environment in food-deprived rats. A qualitatively similar behavioural response wa s induced by PTZ in all the test parameters. AVP and PTZ increased rat brain tribulin activity, the increase in the MAO A inhibitor componen t being more marked than that on the MAO B inhibitor component, conson ant with earlier studies with several anxiogenic agents and anxiety du ring addictive drug withdrawal in rats. The findings indicate that AVP exhibits an anxiogenic effect, unlike the earlier reported anxiolytic effect of atrial natriuretic peptide (ANP), its physiological antagon ist, in rats. The anxiogenic effects of AVP (200 and 500 ng/rat, i.c.v .) and PTZ were inhibited by the benzodiazepine anxiolytic, lorazepam (0.25 mg/kg, i.p.). However, the selective dopamine D-2 receptor antag onist, pimozide (0.5 mg/kg, i.p.), inhibited only the anxiogenic effec t of AVP. The results of the present study indicate that AVP induces s ignificant anxiogenic response in rats which may be dopamine-mediated, like its antidiuretic effect in this species. AVP and ANP have contra ry effects on water homeostasis and may be involved in the syndrome of acute water intoxication seen in psychiatric patients. The present in vestigations suggest that this postulate may hold relevance in view of the opposite effects of AVP and ANP on behaviour.