Antagonism by benzodiazepines of the effects of serotonin-, but not norepinephrine-, uptake blockers in the learned helplessness paradigm in rats.
Benzodiazepines are routinely administered in combination with antidepressant drugs. Such combination can induce pharmacodynamic or pharmacokinetic interactions resulting in either a potentiation or a reduction of the effects of one of the drugs. The present study was undertaken to determine the effects of benzodiazepines alone and in combination with two classes of antidepressant drugs: "specific" norepinephrine uptake blockers (desipramine, maprotiline) and specific serotonin uptake blockers (indalpine, fluvoxamine) in the learned helplessness paradigm in rats. The present results show that daily injection of diazepam (0.2-2 mg/kg) and lorazepam (0.06-0.25 mg/kg) did not reverse the helpless behavior. The reversal of helpless behavior induced by indalpine (1 mg/kg/day) or fluvoxamine (4 mg/kg/day) was antagonized dose-dependently by daily coadministration of benzodiazepines. In contrast, the effects of desipramine (24 mg/kg/day) or maprotiline (48 mg/kg/day) were not modified.
Martin
P
P
Departement de Pharmacologie, Faculte de Medecine Pitie-Salpetriere Universite Paris, France.
Puech
A J
AJ
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006380:Helplessness, Learned; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000378:metabolism*
D000929:Antidepressive Agents, Tricyclic; D001569:Benzodiazepines; D009638:Norepinephrine; D017367:Selective Serotonin Reuptake Inhibitors