Behavioral and prolactin responses to 5-hydroxytryptophan in rats treated during development with 5,7-dihydroxytryptamine.

The serotonin precursor, 5-hydroxytryptophan (5-HTP), can induce a behavioral syndrome characterized by rigidity, splayed feet, tremor, head weaving, salivation and forepaw treading. This response to 5-HTP was markedly potentiated in adult rats treated intracisternally with 5,7-dihydroxytryptamine (5,7-DHT) during development. Prevention of the 5,7-DHT-induced reduction of brain norepinephrine with pargyline or desipramine did not diminish the potentiation of 5-HTP, suggesting that noradrenergic fibers are not contributing to the altered 5-HTP response. It was also found that treatments with 5,7-DHT potentiated the release of prolactin and the disruption of responding in a fixed-ratio operant task induced by 5-HTP. Other experiments indicated that 5,7-DHT treatments potentiated 5-HTP without affecting the action of L-dihydroxyphenylalanine. In addition, administration of the decarboxylase inhibitor, R0-4-4602, at a dose that inhibits enzyme activity in brain, blocked the 5-HTP-induced behavioral syndrome in 5,7-DHT-treated rats, indicating that 5-HTP must be converted to serotonin for 5-HTP to alter behavior. Thus, the present studies indicate that destruction of serotonergic fibers during development can produce permanent changes in central serotonergic mechanisms.