Beneficial Effects of Acute and Repeated Administrations of σ Receptor Agonists on Behavioral Despair in Mice Exposed to Tail Suspension

In an attempt to examine whether σ receptor agonists alleviate behavioral despair, we investigated the effects of σ receptor agonists on the tail suspension-induced immobility in mice. The acute and repeated (14 days) administrations of σ 1 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), σ 1/2 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 σ 1 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 σ, possibly a σ 1 receptor subtype, alleviate behavioral despair, unaccompanied with changes in body weight.