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.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001545:Benserazide / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D004102:Dihydroxytryptamines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology; D011247:Pregnancy; D011292:Premedication; D011388:Prolactin / Q000097:blood*; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism
D004102:Dihydroxytryptamines; D006892:Hydroxydopamines; D011941:Receptors, Adrenergic; D011985:Receptors, Serotonin; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D001545:Benserazide; D011388:Prolactin; D010293:Pargyline; D006916:5-Hydroxytryptophan; D003891:Desipramine; D009638:Norepinephrine