Flunarizine potentiates cocaine-induced dopamine release and motor stimulation in rats.
Pretreatment with flunarizine (20 mg/kg), a diphenylalkylamine calcium channel antagonist, markedly potentiated cocaine (10 mg/kg)-induced dopamine (DA) output from the ventral striatum, as measured by microdialysis in freely moving rats. Moreover, flunarizine enhanced cocaine-induced motor stimulation. Pretreatment with the D2 receptor antagonist (-)-sulpiride (25 mg/kg) potentiated cocaine-induced DA output but, unlike flunarizine, inhibited cocaine-induced motor stimulation. When added to striatal membrane preparations, flunarizine displaced [3H]spiperone binding with a Ki of about 100 nM. Since recent evidence indicates that the effects of cocaine are calcium-dependent and are prevented by dihydropyridine calcium antagonists, these findings suggest that the paradoxical potentiating effect of flunarizine is probably due to an interaction with the DA system and is not due to its calcium antagonist property.
Pani
L
L
B.B. Brodie Department of Neuroscience, University of Cagliari, Italy.
Kuzmin
A
A
Stefanini
E
E
Gessa
G L
GL
Rossetti
Z L
ZL
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004357:Drug Synergism; D005444:Flunarizine / Q000494:pharmacology*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D013134:Spiperone / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology
D011954:Receptors, Dopamine; D013134:Spiperone; D013469:Sulpiride; D003042:Cocaine; D005444:Flunarizine; D004298:Dopamine