Effect of baclofen, a GABAB-agonist, on forced swimming-induced immobility in mice.

The effect of baclofen, a GABAB-agonist, was studied on both forced swimming-induced immobility and isoprenaline-induced enhancement of forced swimming-induced immobility in mice. (+/-) Baclofen (0.5 and 1 mg/kg), and (-) baclofen (0.5, 1 and 2 mg/kg) attenuated forced swimming-induced immobility. The effect of baclofen was not reversed by bicuculline, a GABAA-antagonist. Baclofen also reduced isoprenaline-induced enhancement of forced swimming-induced immobility. On concomitant administration of a subeffective dose of baclofen with a subeffective dose of propranolol, desipramine and amitriptyline, a potentiating effect was observed. These results are corroborative of our previous finding that GABAergic agents, particularly GABAB-receptors, play a role in the modulation of despair behavior in mice and in the action of antidepressant drugs. Baclofen (5 mg/kg) did not produce any significant effect on forced swimming-induced immobility, but reduced significantly the locomotor activity of the animals. Lower doses (0.5 and 1 mg/kg) of baclofen, which reduced the forced swimming-induced immobility, did not affect the locomotor activity. At higher and lower tissue concentrations of the drug, involvement of different receptor populations is suggested.