Increased tonic activation of rat forebrain 5-HT(1A) receptors by lithium addition to antidepressant treatments.
The present study was undertaken to determine whether lithium addition to long-term treatment with different classes of antidepressant drugs could induce a greater effect on the serotonin (5-HT) system than the drugs given alone. Because 5-HT(1A) 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-HT(1A) 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 microg/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 microg/kg of WAY 100635 was needed to increase significantly the firing activity of these neurons. On the other hand, WAY 100635, at a dose of only 25 microg/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.
Haddjeri
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Neurobiological Psychiatry Unit, McGill University, 1033 Pine Avenue West, Montréal, PQ, Canada.
Szabo
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ST
de Montigny
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C
Blier
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P
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D003866:Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology; D004359:Drug Therapy, Combination; D016166:Free Radical Scavengers / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D007099:Imipramine / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D017374:Paroxetine / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000494:pharmacology; D014191:Tranylcypromine / Q000494:pharmacology
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D016166:Free Radical Scavengers; D008996:Monoamine Oxidase Inhibitors; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D014191:Tranylcypromine; D017374:Paroxetine; D008094:Lithium; D007099:Imipramine