Perinatal exposure to 5-metoxytryptamine, behavioural-stress reactivity and functional response of 5-HT1A receptors in the adolescent rat

Serotonin is involved in a wide range of physiological and patho-physiological mechanisms. In particular, 5-HT1A receptors are proposedto mediate stress-adaptation. The aim of this research was to investigate in adolescent rats: first, the consequences of perinatal exposure to 5-metoxytryptamine (5MT), a 5-HT1/5-HT2 serotonergic agonist, on behavioural-stress reactivity in elevated plus maze, open field and forced swimtests; secondly, whether the behavioural effects induced by perinatal exposure to 5MT on open field and forced swim tests were affected by theselective 5-HT1A receptor agonist LY 228729, a compound able to elicit a characteristic set of motor behaviours on these experimental models,and by the co-administration of the selective and silent 5-HT1A antagonist WAY 100635. Results indicate that a single daily injection of 5MT to,pregnant dams from gestational days 12 to 21 (1 mg/kg s.c.), and to the pups from postnatal days 2 to 18 (0.5 mg kg s.c.), induce in the adolescent ratoffspring: an increase in the percentage of entries and time spent on the open arms in the elevated plus maze; a reduction in locomotor activity andrearing frequency, and an increase in the time spent on the central areas in the open field test; a decrease in immobility and an increase in swimmingin the forced swim test. Acute administration of LY 228729 (1.5 mg/kg s.c.) strongly decreases rearing frequency and increases peripheral activityin the open field test, and decreases immobility and increases swimming in the forced swim test both in perinatally vehicle and 5MT-exposedoffspring. Co-administration of WAY 100635 (0.25 mg/kg s.c.) abolishes the effects exerted by LY 228729. These results suggest that, in theadolescent rat, perinatal exposure to 5MT enhances the stress-related adaptive behavioural responses, presumably through a predominant action onpresynaptic 5-HT1A receptors and does not deteriorate the functional response of 5-HT1A receptors to selective agonist and antagonist compounds.