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-HTlA sites in the rat brain by autoradiography and membrane binding, using the selective ligand [3H18-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT1, following long-term antidepressant treatment. Following a 21-day treatment with amitriptyline (10 mg/kg/day), there was a significant increase of L3H18-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 L3H18-OH-DPAT. Conversely, fluoxetine (10 mg/kg/day), a selective blocker of 5-HT reuptake, and gepirone (10 mg/kg/day), a 5-HTlA agonist, both administered for 21 days, significantly reduced L3H18-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 L3H18-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-HTlA receptors might underlie the enhancement of 5-HT neurotransmission by antidepressant treatments.
5-HTlA Receptors, Antidepressants, Anxiolytics