Behavioral effects of L-5-hydroxytryptophan after destruction of ascending serotonergic pathways in the rat: the role of catecholaminergic neurons.
Lesions in the medial forebrain bundle of the rat produced a 68 to 74% decrease in telencephalic serotonin (5-HT) and a 30 to 43% decrease in jump threshold. L-5-Hydroxytryptophan (L-5-HTP; 37.5 mg/kg) returned the 5-HT content and jump threshold of lesioned rats to normal levels. These effects of L-5-HTP were also observed after the inhibition of extracerebral decarboxylase activity with Ro 4-4602 (50 mg/kg). Pretreatment with 6-hydroxydopamine (6-OHDA), which selectively destroys catecholamine neurons, had no effect on the jump threshold of nonlesioned rats nor did it further change the 5-HT content or jump threshold of lesioned rats. Lesioned rats pretreated with 6-OHDA demonstrated an increase in 5-HT content after L-5-HTP; however, their jump threshold remained significantly lower than that of controls. This ability of 6-OHDA to block the behavioral effects of L-5-HTP in lesioned rats was also observed after Ro 4-4602. In rats given Ro 4-4602, the accumulation of 5-HT at 90 minutes after injection of L-5-HTP was significantly correlated (r = 0.98) with total monoamine content. Thus, 6-OHDA pretreatment significantly decreased the net accumulation of 5-HT from L-5-HTP in nonlesioned rats. These rats also demonstrated further decreases in norepinephrine and dopamine content after L-5-HTP. It was concluded that L-5-HTP can be decarboxylated to 5-HT in serotonergic and catecholaminergic neurons and that the behavioral effects of L-5-HTP in lesioned rats may be due to the formation of 5-HT in catecholaminergic neurons where it may act as a "false-transmitter."
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001545:Benserazide / Q000494:pharmacology; D001679:Biogenic Amines / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002395:Catecholamines / Q000502:physiology*; D004597:Electroshock; D006892:Hydroxydopamines / Q000494:pharmacology; D007031:Hypothalamus / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000502:physiology*; D051381:Rats; D013687:Telencephalon / Q000378:metabolism
D001679:Biogenic Amines; D002395:Catecholamines; D006892:Hydroxydopamines; D001545:Benserazide