Effects of bulbectomy and subsequent antidepressant treatment on brain 5-HT2 and 5-HT1A receptors in mice.

The effects of bilateral olfactory bulbectomy on serotonergic 5-HT2 and 5-HT1A receptor binding were studied in the frontal cortex (FC), limbic structures (LS), including the hippocampus, amygdala, olfactory tubercule, and piriform cortex, and hypothalamus (HTH) in mice. Bulbectomy resulted in the increase of Bmax for [3H]spiperone binding with 5-HT2 receptors in FC in C57Bl/6j. The receptors in LS and HTH remained unchanged. Subchronic treatment of the bulbectomized mice with antidepressant trazodone (20 mg/kg/day, IP, 14 days) induced downregulation of 5-HT2 receptors in FC and LS. The other two antidepressants used, amitriptyline (20 mg/kg/day, IP, 14 days) and imipramine (10 mg/kg/day, IP, 14 days), did not alter these receptors. [3H]8-OH-DPAT binding with 5-HT1A receptors was not altered by bulbectomy in any brain area in C57Bl/6j mice. Amitriptyline and trazodone decreased Bmax for these receptors in FC in the bulbectomized mice while imipramine was ineffective. Amitriptyline and imipramine significantly increased Bmax and decreased Kd in HTH, and trazodone displayed the same tendency. Bulbectomy did not alter 5-HT2 receptors in DBA/2j mice. Amitriptyline increased Kd in the all brain areas without changing Bmax in the bulbectomized DBA/2j mice. Trazodone significantly decreased Bmax in FC and increased Kd in FC and LS. Imipramine decreased Bmax while increasing Kd in LS. The possible involvement of the serotonin receptor subtypes in the bulbectomy-induced behavioral deficits and in the restorative action of the antidepressants is discussed.