Autoradiographic quantification of serotonin1A receptors in rat brain following antidepressant drug treatment.
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-HT1A sites in the rat brain by autoradiography and membrane binding, using the selective ligand [3H]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 [3H]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 [3H]8-OH-DPAT. Conversely, fluoxetine (10 mg/kg/day), a selective blocker of 5-HT reuptake, and gepirone (10 mg/kg/day), a 5-HT1A agonist, both administered for 21 days, significantly reduced [3H]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 [3H]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-HT1A receptors might underlie the enhancement of 5-HT neurotransmission by antidepressant treatments.
Welner
S A
SA
Douglas Hospital Research Centre, Montreal, Quebec, Canada.
De Montigny
C
C
Desroches
J
J
Desjardins
P
P
Suranyi-Cadotte
B E
BE
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000378:metabolism
D000928:Antidepressive Agents; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D005473:Fluoxetine; D000639:Amitriptyline; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin