Dopaminergic and opioidergic mediations of tricyclic antidepressants in the learned helplessness paradigm

The roles of dopaminergic and opioid neurotransmissions in the activity of three tricyclic antidepressants endowed with different monoamine-reuptake properties [desipramine (DESI), imipramine (IMI), amineptine (AMN)] were examined using a behavioral model of depression in rats; the learned helplessness paradigm. In this model, exposure of rats to inescapable shocks (day 1) produced a subsequent escape deficit in a shuttle box test (days 3, 4, and 5). The escape deficit was reversed by AMN, DESI, and IMI administered twice daily for 5 days (16 and 32 mg/kg/day, p < 0.05, days 3, 4, and 5). In addition, AMN tended to enhance the motor activity of rats during the intertrial intervals, but on the first shuttle-box test only (day 3: p < 0.05, control vs AMN). Haloperidol, a preferential D-2 dopamine receptor antagonist, acutely injected IP (37.5 mu g/kg), suppressed the behavioral activity of DESI and IMI but not that of AMN. Naloxone, a preferential mu-opioid receptor antagonist, acutely injected IP (0.5 mg/kg), suppressed the behavioral activity of IMI but not that of DESI and AMN. It is concluded that an increased dopaminergic activity is a neurochemical effect common to the different tricyclic antidepressants (via a presynaptic mechanism for AMN and a postsynaptic mechanism for DESI and IMI), whereas an increased mu-opioid neurotransmission does not appear to be essential. (C) 1999 Elsevier Science Inc.