Beneficial effects of acute and repeated administrations of sigma receptor agonists on behavioral despair in mice exposed to tail suspension.

In an attempt to examine whether sigma receptor agonists alleviate behavioral despair, we investigated the effects of sigma receptor agonists on the tail suspension-induced immobility in mice. The acute and repeated (14 days) administrations of sigma1 receptor agonists, such as 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride (SA4503) (1 and/or 3 mg/kg) and (+)-pentazocine (5.6 mg/kg), sigma1/2 receptor agonists, such as 1,3-di(2-tolyl)guanidine (DTG) (3 and/or 5.6 mg/kg), desipramine (7.5 and/or 15 mg/kg), and fluoxetine (10 and/or 20 mg/kg), reduced immobility in mice exposed to tail suspension. N,N-Dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl] ethylamine monohydrochloride (NE-100), a sigma1 receptor antagonist, significantly antagonized the decrease in immobility induced by acute administrations of SA4503 (1 mg/kg) and (+)-pentazocine (5.6 mg/kg). Although not significant, NE-100 showed a tendency to inhibit the DTG (5.6 mg/kg)-induced decrease in immobility. In contrast, repeated administrations of SA4503 (1 and 3 mg/kg), (+)-pentazocine (5.6 mg/kg) or DTG (5.6 mg/kg) failed to affect the increase in body weight. These results suggest that acute and repeated stimulations of sigma, possibly a sigma1 receptor subtype, alleviate behavioral despair, unaccompanied with changes in body weight.