Chronic valproate fails to prevent imipramine-induced behavioural sensitization to the dopamine D2-like receptor agonist quinpirole.
Based on experimental evidence suggesting a relationship between dopamine and mania, we proposed the antidepressant-induced dopaminergic supersensitivity as a model of antidepressant-related mania. We have previously shown the ability of carbamazepine, but not lithium, to prevent this phenomenon. Here we show that sodium valproate (50 mg/kg/day for 3 weeks) fails to prevent imipramine (20 mg/kg/day for 3 weeks)-induced sensitization to the locomotor response to the dopamine D2-like receptor agonist quinpirole (0.15 mg/kg). Since lithium, carbamazepine and valproate are all considered poorly effective in the treatment of antidepressant-related mania, the validity of the proposed model should be disproved by the carbamazepine results, to which, however, a pharmacokinetic mechanism might have concurred.
Dipartimento di Scienze del Farmaco, Università di Sassari, via Muroni 23/a, 07100 Sassari, Italy. dsfpaolo@uniss.it
Paolo S
PS
D'Aquila
Francesca
F
Panin
Gino
G
Serra
D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D014635:Valproic Acid / Q000494:pharmacology*
D000927:Anticonvulsants; D000929:Antidepressive Agents, Tricyclic; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D014635:Valproic Acid; D007099:Imipramine