Effects of desipramine on regional serotonin synthesis in the rat brain: acute and chronic autoradiographic studies.
Various studies have implicated the involvement of noradrenaline (NA) and/or serotonin (5-hydroxytryptamine (5-HT)) in the pathogenesis and treatment of depression. The aim of the present study was to investigate the effects of acute and 7 days of administration of desipramine, a NA re-uptake inhibitor, on the rate of 5-HT synthesis in the rat brain. The study was done by an autoradiographic method using alpha-[14C]-methyl-L-tryptophan as a tracer. The acute (10mg/kg, i.p., 2h before i.v. infusion of the tracer) or 7 days of desipramine (10mg/kg per day, i.p.) did not affect plasma tryptophan (Trp) concentrations, as compared to control (saline treated) rats. Acute treatment with desipramine decreased the rate of 5-HT synthesis in the brain regions that contain 5-HT cell bodies between 19 and 28%, and increased the rate of 5-HT synthesis in the majority of areas containing 5-HT terminals between 21 and 65%. In contrast to the acute treatment, a 7-day administration increased 5-HT synthesis rates in the dorsal raphe (24%), but decreased it in raphe magnus (35%), superior olive (45%), caudate (31%), superior (38%) and inferior (53%) colliculus, and in the auditory cortex (35%). This suggests that the effect of desipramine on 5-HT synthesis rate is time-dependent and differs in the cell bodies and structures containing 5-HT nerve terminals.
Pivac
Nela
N
Cone Neurosurgical Research Laboratory, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, 3801 University St., Montreal, Que., Canada H3A 2B4.
Mück-Seler
Dorotea
D
Diksic
Mirko
M
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000096:biosynthesis*; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000097:blood
D018759:Adrenergic Uptake Inhibitors; C020774:alpha-methyltryptophan; D012701:Serotonin; D014364:Tryptophan; D003891:Desipramine