Dopamine, opioids and learned helplessness (original) (raw)

Dopaminergic and opioidergic mediations of tricyclic antidepressants in the learned helplessness paradigm
by
Besson A, Privat AM, Eschalier A, Fialip J
NeuroPsychoPharmacologie,
Universite d'Auvergne,
Laboratoire de Pharmacologie,
Faculte de Pharmacie,
Clermont Ferrand, France.
Life Sci, 1992, 51:10, 711-8

ABSTRACT

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.

Structure Metabolism Pharmacology Amineptine excess Amineptine and sex Mesolimbic dopamine Amineptine and the rat Dopaminergic fast actors Amineptine and smart mice Amineptine and smarter dogs Opioids, depression and learned helplessness

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