Noradrenergic and opioid mediation of tricyclic-induced reversal of escape deficits caused by inescapable shock pretreatment in rats.

The present study was undertaken to investigate the possible involvement of a noradrenergic and opioid mediation of the reversal by tricyclic antidepressants of escape deficits produced by inescapable shock pretreatment. Rats were first exposed to 60 inescapable shocks (15 s duration, 0.8 mA, every min +/- 15 s) and 48 h later subjected, to daily shuttle-box sessions (30 trials/day, ITI: 30 s) during 3 consecutive days. Twice-daily IP injection of desipramine or clomipramine (total daily dose: 32 mg/kg) prevented escape deficits. Penbutolol (0.125; 0.25; 0.5 mg/kg), prazosin (1; 2 mg/kg) and naloxone (0.5; 1 mg/kg) given once a day dose-dependently attenuated the beneficial effect of tricyclic antidepressants in reducing the number of escape failures in rats exposed to shock pretreatment. In agreement with data obtained in the forced-swimming model, these findings support the notion that activation of noradrenergic and opioid receptors is an important factor in the mediation of the effects of tricyclic antidepressants in animal models of depression.