Actions of nimodipine on the serotonergic systems of rat brain.
1. The effects of the serotonin (5-HT) precursor, L-5-hydroxytryptophan (L-5-HTP), or the selective 5-HT1A receptor agonist, 8-OHDPAT, on behavior or brain 5-HT metabolism or both were evaluated in rats IP pretreated with nimodipine at doses ranging from 0.31 to 40 mg/kg. 2. Nimodipine, in a wide dose range (0.6-20.0 mg/kg) potentiated the head-twitch response to L-5-HTP. 3. The effects of nimodipine on the 5-HT metabolism of rats treated with L-5-HTP did not comply with the increase in the behavioral response to this 5-HT precursor. 4. Nimodipine antagonized the effects on 5-HT metabolism induced by 8-hydroxy-2-(di-N-propyl-amino)-tetralin through stimulation of 5-HT1A autoreceptors. 5. It was concluded that the effects of nimodipine on brain 5-HT metabolism appeared to be linked to activation of serotonergic neurotransmission likely due to inhibition of the back-regulation mechanism mediated by presynaptic 5-HT1A receptors.
Gaggi
R
R
Department of Pharmacology, University of Bologna, Italy.
Dall' Olio
R
R
Santangelo
M
M
Roncada
P
P
D006916:5-Hydroxytryptophan / Q000378:metabolism; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017661:Receptors, Presynaptic / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D017661:Receptors, Presynaptic; D017366:Serotonin Receptor Agonists; D014665:Vasodilator Agents; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D009553:Nimodipine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006916:5-Hydroxytryptophan