Dopaminergic function in rat brain after oral administration of calcium-channel blockers or haloperidol. A microdialysis study.
Microdialysis technique was used to study the effects of both acute and repeated oral administration of calcium-channel blockers (flunarizine, cinnarizine, verapamil, nifedipine and nicardipine) in dopaminergic function in rat brain and to compare them to the effects of haloperidol. Acute flunarizine, nicardipine or haloperidol increased extracellular levels of dopamine (DA) or metabolites. After repeated (18 days) administration, nicardipine, nifedipine, verapamil or haloperidol increased and flunarizine decreased extracellular striatal levels of dopamine or metabolites. Chronic treatment with calcium-channel blockers or haloperidol failed to block K(+)-evoked release of dopamine. This suggests that the calcium-channel blockers used in this study do not influence calcium entry necessary for DA release. An acute challenge with haloperidol caused either no change or a decrease in extracellular levels of DA or metabolites after repeated administration of calcium-channel blockers or haloperidol. This is considered to be due to the lesser response of dopaminergic neurons because of treatment. A neuroleptic-like mechanism of action together with a decrease in firing activity and/or a reduced dopamine re-uptake of dopaminergic neurons are considered.
Reiriz
J
J
Biochemistry Unit, School of Medicine, Hospital Clinico y Provincial, Barcelona, Spain.
Ambrosio
S
S
Cobos
A
A
Ballarín
M
M
Tolosa
E
E
Mahy
N
N
D000200:Action Potentials / Q000187:drug effects; D000284:Administration, Oral; D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D005110:Extracellular Space / Q000737:chemistry; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*
D002121:Calcium Channel Blockers; D006220:Haloperidol; D002118:Calcium; D004298:Dopamine