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Autoradiographic quantification of serotonin 1A receptors in rat brain following antidepressant drug treatment
Author(s) -
Welner S. A.,
De Montigny C.,
Desroches J.,
Desjardins P.,
SuranyiCadotte B. E.
Publication year - 1989
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890040410
Subject(s) - dorsal raphe nucleus , chemistry , pharmacology , medicine , serotonergic , endocrinology , agonist , antidepressant , raphe nuclei , hippocampus , 5 ht receptor , receptor , serotonin , biology
Abstract There is growing evidence that the serotonergic (5‐HT) system is involved in the pathogenesis and treatment of major depression. The 5‐HT receptor subtype involved in the enhancing effect of antidepressant treatments, however, has not been identified. The present study was undertaken to quantify 5‐HT 1A sites in the rat brain by autoradiography and membrane binding, using the selective ligand [ 3 H]8‐hydroxy‐N, N‐dipropyl‐2‐aminotetralin (8‐OH‐DPAT), following long‐term antidepressant treatment. Following a 21‐day treatment with amitriptyline (10 mg/kg/day), there was a significant increase of [ 3 H]8‐OH‐DPAT binding measured by autoradiography in the dorsal hippocampus, but there was no change in the nucleus raphe dorsalis; whole brain membrane binding revealed an increase in the number of binding sites, with no change in the affinity for [ 3 H]8‐OH‐DPAT. Conversely, fluoxetine (10 mg/kg/day), a selective blocker of 5‐HT reuptake, and gepirone (10 mg/kg/day), a 5‐HT 1A agonist, both administered for 21 days, significantly reduced [ 3 H]8‐OH‐DPAT binding measured by autoradiography in the nucleus raphe dorsalis without altering hippocampal binding sites. The control active treatment with diazepam (2 mg/kg/day) did not alter [ 3 H]8‐OH‐DPAT binding in the hippocampus or in the nucleus raphe dorsalis. All groups were compared to a 21‐day vehicle‐treated control group. These results are fully consistent with previous electrophysiological and behavioral studies and suggest that alterations of 5‐HT 1A receptors might underlie the enhancement of 5‐HT neurotransmission by antidepressant treatments.