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 D2 dopamine receptor antagonist, acutely injected IP (37.5 microg/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.
Besson
A
A
NeuroPsychoPharmacologie, Université d'Auvergne, Laboratoire de Pharmacologie, Faculté de Pharmacie, Clermont Ferrand, France.
Privat
A M
AM
Eschalier
A
A
Fialip
J
J
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004347:Drug Interactions; D004924:Escape Reaction / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D006380:Helplessness, Learned; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D018759:Adrenergic Uptake Inhibitors; D000929:Antidepressive Agents, Tricyclic; D003986:Dibenzocycloheptenes; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D009292:Narcotic Antagonists; D018847:Opioid Peptides; C011597:amineptin; D009270:Naloxone; D006220:Haloperidol; D007099:Imipramine; D003891:Desipramine; D004298:Dopamine