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.
Pharmacol Biochem Behav 1999 Nov; 64(3):541-8

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.

TCAs
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Imipramine
Amineptine
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Desipramine
TCAs v SSRIs
Antidepressants
Retarded depression
Antidepressant toxicity
Selectivity or multiplicity?
Imipramine and dopamine d1
Tricyclic antidepressants for depression
SSRIs compared with tricyclic antidepressants
Desipramine (Norpramin, Pertofrane) and mu-opioid receptors

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