Acute reserpine treatment increases rat brain serotonin synthesis via a nerve impulse-dependent mechanism.
Notwithstanding recent advances in the understanding of central serotonin (5-HT) function, important basic aspects of the control of brain 5-HT neuronal transmission remain incompletely elucidated. The present experiments addressed the putative mechanism(s) by which acute reserpine treatment stimulates cerebral 5-HT synthesis; also, such studies might shed further light on the relation between impulse flow and transmitter synthesis in central 5-HT neurons. Reserpine (5 mg/kg, i.p., 90 min before death) markedly elevated 5-HT synthesis [5-hydroxytryptophan (5-HTP) accumulation after decarboxylase inhibition by means of NSD 1015] in the limbic, striatal, and cortical rat brain parts. Hemitransection of ascending neuronal connections between the brainstem and the forebrain, performed immediately before reserpine injection, did not affect the 5-HT synthesis per se but completely prevented the drug response on the lesioned side. Similarly, systemic administration of the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (0.1 mg/kg, s.c., 60 min before death) blocked the reserpine-induced elevation of brain 5-HT synthesis. These findings indicate that the reserpine-induced rise in axon terminal 5-HTP accumulation is dependent on intact (5-HT) neuronal impulse flow, which may or may not involve a transient impairment of somatodendritic 5-HT release and, in turn, autoreceptor tone.
Hjorth
S
S
Department of Pharmacology, University of Göteborg, Sweden.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D003714:Denervation / Q000379:methods; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology*; D012701:Serotonin / Q000096:biosynthesis*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D013764:Tetrahydronaphthalenes; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D012110:Reserpine