Dopaminergic and Opioidergic Mediations of Tricyclic Antidepressants in the Learned Helplessness Paradigm

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 1999-11, Vol.64 (3), p.541-548
• Main Authors: Besson, A., Privat, A.M., Eschalier, A., Fialip, J.
• Format: Article
• Language: English
• Subjects: Adrenergic Uptake Inhibitors - pharmacology; amineptine; Animals; Antidepressants; Antidepressive Agents, Tricyclic - pharmacology; Behavioral psychophysiology; Biological and medical sciences; Desipramine - pharmacology; Dibenzocycloheptenes - pharmacology; Dopamine; Dopamine - physiology; Dopamine Antagonists - pharmacology; Dopamine D2 Receptor Antagonists; Drug Interactions; Escape Reaction - drug effects; Fundamental and applied biological sciences. Psychology; Haloperidol; Haloperidol - pharmacology; Helplessness, Learned; imipramine; Imipramine - pharmacology; Learned helplessness; Male; Medical sciences; Motor Activity - drug effects; Naloxone - pharmacology; Narcotic Antagonists - pharmacology; Neuropharmacology; Neurotransmission and behavior; Opioid; Opioid Peptides - physiology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopharmacology; Rat; Rats; Rats, Wistar
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/S0091-3057(99)00102-1

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 μg/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.