Increased tonic activation of rat forebrain 5-HT1A receptors by lithium addition to antidepressant treatments

The present study was undertaken to determine whether lithium addition to l ong-term treatment with different classed of antidepressant drugs could ind uce a greater effect on the serotonin (5-HT) system than the drugs given al one. Because 5-HT1A receptor activation hyperpolarizes and inhibits the fir ing activity of CA(3) pyramidal neurons in the dorsal hippocampus, the degr ee of disinhibition produced by the selective 5-HT1A receptor antagonist WA Y 100635 was determined using in vivo extracellular recordings. In controls , as well as in rats receiving a lithium diet for 3 days, the administratio n of WAY 100635(25-100 mu g/kg, IV) did not modify the firing activity of d orsal hippocampus CA(3) pyramidal neurons. When the tricyclic antidepressan t imipramine (10 mg/kg/day, SC), the monoamine oxidase inhibitor tranylcypr omine (2.5 mg/kg/day, SC) and the selective 5-HT reuptake inhibitor paroxet ine (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 activit y 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 i n rats receiving both a long-term antidepressant treatment and a short-term lithium diet. It is concluded that the addition of lithium to antidepressa nt treatments produced a greater disinhibition of dorsal hippocampus CA(3) pyramidal neurons than any treatments given alone. The present results supp ort 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. Pu blished by Elsevier Science Inc.