Shuttle-box deficits induced by inescapable shocks in rats: reversal by the beta-adrenoreceptor stimulants clenbuterol and salbutamol.

Beta-adrenoreceptor stimulants such as salbutamol and clenbuterol have been reported to be effective in depressive states and to share many actions with classical antidepressants in animals. To further explore the antidepressant activity of these drugs, we investigated their effects in rats subjected to helplessness training. Rats were first exposed to inescapable shock pre-treatment (60 shocks, 15 sec duration, 1 mA every minute +/- 15 sec) and 48 hr later, shuttle-box training (30 trials/day, ITI: 30 sec) was initiated in order to evaluate escape and avoidance deficits. Rats pretreated with inescapable shocks exhibited escape and avoidance deficits when tested for subsequent responding in a shuttle-box. The deficits are particularly marked at the third training session. Daily IP injections of clenbuterol (total daily dose: 0.5 and 0.75 mg/kg) and salbutamol (16 and 24 mg/kg) prevented escape deficits as did daily injections of classical antidepressants such as desipramine (16 and 24 mg/kg/day) and clomipramine (16 and 24 mg/kg/day). These data extend previous results bearing on the similarity of action of beta receptor stimulants and tricyclic antidepressants and further support the notion of a close relationship between noradrenergic function, more especially beta-adrenoreceptors, and "helpless" behavior.