Abstract
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-HT1A receptor activation hyperpolarizes and inhibits the firing activity of CA3 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 μg/kg, IV) did not modify the firing activity of dorsal hippocampus CA3 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 μg/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 μg/kg, increased significantly the firing rate of CA3 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 CA3 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.
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Acknowledgements
This work was supported in part by the Medical Research Council of Canada (MRC) Grants (MT-11014 and MA-6444 to P.B. and C. de M., respectively). N.H. is in receipt of a fellowship from the Royal Victoria Hospital Research Institute, S.T.S. is in receipt of a studentship from the “Fonds pour la Formation de Chercheurs et l'Aide à la Recherche,” and P. B. of a MRC Scientist Award
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Haddjeri, N., Szabo, S., de Montigny, C. et al. Increased Tonic Activation of Rat Forebrain 5-HT1A Receptors by Lithium Addition to Antidepressant Treatments. Neuropsychopharmacol 22, 346–356 (2000). https://doi.org/10.1016/S0893-133X(99)00138-4
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DOI: https://doi.org/10.1016/S0893-133X(99)00138-4
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