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 an d repeated oral administration of calcium-channel blockers (flunarizin e, cinnarizine, verapamil, nifedipine and nicardipine) in dopaminergic function in rat brain and to compare them to the effects of haloperid ol. Acute flunarizine, nicardipine or haloperidol increased extracellu lar levels of dopamine (DA) or metabolites. After repeated (18 days) a dministration, nicardipine, nifedipine, verapamil or haloperidol incre ased and flunarizine decreased extracellular striatal levels of dopami ne or metabolites. Chronic treatment with calcium-channel blockers or haloperidol failed to block K+-evoked release of dopamine. This sugges ts that the calcium-channel blockers used in this study do not influen ce calcium entry necessary for DA release. An acute challenge with hal operidol 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 r esponse of dopaminergic neurons because of treatment. A neuroleptic-li ke mechanism of action together with a decrease in firing activity and /or a reduced dopamine re-uptake of dopaminergic neurons are considere d.