Lithium enhancement of central 5-HT transmission induced by 5-HT precursors.
The effects of acute and chronic lithium chloride administration on synaptic transmission between bulbospinal norepinephrine (NE) or 5-hydroxy-tryptamine (5-HT) pathways and sympathetic preganglionic neurons were tested in unanesthetized, spinal cats. Discharges recorded from sympathetic preganglionic white rami were evoked by stimulation of spinal reflex pathways or descending excitatory pathways in the cervical spinal cord. Acute lithium administration (2 meq/kg) produced insignificant depression of the reflex pathway but markedly depressed transmission through the intraspinal pathway, an effect that was prevented by depletion or blockage of 5-HT. These observations and the failure of lithium to alter the typical effects of L-dopa on both pathways indicate that lithium does not affect transmission through the excitatory NE pathway. L-Tryptophan (1,0 mg/kg) alone produced little or no depression of either pathway, but 3--4 hr after lithium, this dose of L-tryptophan gradually depressed transmission through both pathways by about 20%. After chronic lithium pretreatment (1 meq/kg twice a day for 3 days), L-tryptophan rapidly depressed transmission through spinal reflex and intraspinal pathways by 40% and 50% respectively. Chronic lithium pretreatment also more than doubled the depression of transmission through both pathways produced by 30 mg/kg of 5-HTP. The average of plasma lithium levels 8--10 hr after the last chronic dose was 1.5 meq/liter. These results support the proposal that lithium increases the uptake of L-tryptophan and 5-HTP by central 5-HT terminals and thereby enhances 5-HT synthesis which is reflected in increased transmission at central 5-HT synapses.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000187:drug effects; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D007367:Intercostal Nerves / Q000187:drug effects; D007980:Levodopa / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D008526:Medulla Oblongata / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D012018:Reflex / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D014364:Tryptophan / Q000494:pharmacology*
D012701:Serotonin; D007980:Levodopa; D014364:Tryptophan; D008094:Lithium; D006916:5-Hydroxytryptophan; D009638:Norepinephrine