Increased tonic activation of rat forebrain 5-HT(1A) receptors by lithium addition to antidepressant treatments.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Haddjeri, N; Szabo, ST; de Montigny, C; Blier, P

Published Date

  • April 2000

Published In

Volume / Issue

  • 22 / 4

Start / End Page

  • 346 - 356

PubMed ID

  • 10700654

Pubmed Central ID

  • 10700654

International Standard Serial Number (ISSN)

  • 0893-133X

Digital Object Identifier (DOI)

  • 10.1016/S0893-133X(99)00138-4


  • eng

Conference Location

  • England