Journal
NEUROPSYCHOPHARMACOLOGY
Volume 22, Issue 4, Pages 346-356Publisher
NATURE PUBLISHING GROUP
DOI: 10.1016/S0893-133X(99)00138-4
Keywords
lithium; imipramine; tranylcypromine; paroxetine; WAY 100635; 5-HT1A receptors; dorsal hippocampus
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The present study was undertaken to determine whether lithium addition to long-term treatment with different classed of antidepressant drugs could induce a greater effect on the serotonin (5-HT) system than the drugs given alone. Because 5-HT1A receptor activation hyperpolarizes and inhibits the firing activity of CA(3) pyramidal neurons in the dorsal hippocampus, the degree of disinhibition produced by the selective 5-HT1A receptor antagonist WAY 100635 was determined using in vivo extracellular recordings. In controls, as well as in rats receiving a lithium diet for 3 days, the administration of WAY 100635(25-100 mu g/kg, IV) did not modify the firing activity of dorsal hippocampus CA(3) pyramidal neurons. When the tricyclic antidepressant imipramine (10 mg/kg/day, SC), the monoamine oxidase inhibitor tranylcypromine (2.5 mg/kg/day, SC) and the selective 5-HT reuptake inhibitor paroxetine (10 mg/kg/day, SC) were administered alone for 21 days, a dose of 50 mu g/kg of WAY 100635 was needed to increase significantly the firing activity of these neutrons. On the other hand, WAY 100635, at a dose of only 25 mu g/kg, increased significantly the firing rate of CA(3) pyramidal neurons in rats receiving both a long-term antidepressant treatment and a short-term lithium diet. It is concluded that the addition of lithium to antidepressant treatments produced a greater disinhibition of dorsal hippocampus CA(3) pyramidal neurons than any treatments given alone. The present results support the notion that the addition of lithium to antidepressants may produce a therapeutic response in treatment-resistant depression by enhancing 5-HT neurotransmission. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.
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