Physical exercise as a novel antidepressant agent: possible role of serotonin receptor subtypes

Long-term exercise is associated with an antidepressant effect in patients with mild to moderate forms of nonbipolar depression and appears to be a promising new approach to its treatment. Adaptive changes in serotonin (5-HT) receptor functioning appears to play an important role in mediating the action of various antidepressant treatments. We investigated the adaptive changes in behavioral sensitivity of the 5-HT receptor subtype following 4 weeks of swimming exercise in normal rats, as well as in an animal model of depression (3 week, variety of chronic stressors). 5-HT1A autoreceptor sensitivity was assessed by hyperphagic response induced by 8-OH-DPAT (0.25 mg/kg, IP); 5-HT1A postsynaptic receptor by 5-HT syndrome induced by 8-OH-DPAT (0.75 mg/kg, IP), and 5 Me-ODMT (5 mg/kg, IP); and 5-HT2 receptor by wet dog shakes response induced by quipazine (1 mg/kg, IP) and 5MeODMT (5 mg/kg, IP). It was observed that exercise training in normal rats resulted in enhanced sensitivity of the 5-HT2 receptors along with subsensitivity of 5-HT1A autoreceptors. Exercise, given prophylactically along with chronic stressors, was able to prevent the development of behavioral deficit in the open-field test, and the animals developed remarkably enhanced sensitivity of 5-HT2 receptors. This adaptive supersensitivity of 5-HT2 receptor is also seen after various antidepressant treatments and may play an important role in mediating the antidepressant action of exercise.