Effects of acute and chronic systemic administration of some typical antipsychotic drugs on turnover of dopamine and potassium ion-induced release of dopamine in the striatum of the rat in vivo.
Chronoamperometry was used to measure the dose dependency of antipsychotic drug (spiperone, haloperidol and chlorpromazine)-induced increases in depolarization-stimulated release of dopamine in the striatum of the rat in vivo. The dose-response curves were found to be at least biphasic (small doses increased release and large doses inhibited release) and different in shape from dose-response curves for increases in the turnover of dopamine, suggesting that the two processes may not be related. The threshold dose to induce increased depolarization-stimulated release of dopamine correlated with the values in the literature for doses required to block stereotype induced by apomorphine and amphetamine and doses sufficient to cause a maximal increase in release correlated with the doses required for the induction of catalepsy. In addition, the ratio of the doses required to obtain half-maximal and maximal increases in stimulated release of dopamine, matched values in the literature of the ratio of doses required to ameliorate psychotic symptoms, whereas the doses required to reverse the increase induced by antipsychotic drugs did not. Chronic administration of haloperidol resulted in alterations in the dose-response curves for both the release and turnover of DA. Chronic administration caused a reversal of the effect of acute administration in the small dose range (inhibition as opposed to enhancement of release), a decrease in the maximum magnitude of release of dopamine obtained and an overall shift to the right of the dose-response curve. Chronic administration of haloperidol decreased turnover, relative to animals receiving the drug acutely and no shift in the position of the dose-response curve was observed.
Department of Biochemistry and Biophysics, Washington State University, Pullman 99164-4630.
T A
TA
Patterson
J O
JO
Schenk
D000818:Animals; D001711:Biotransformation; D002746:Chlorpromazine / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011188:Potassium / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013134:Spiperone / Q000008:administration & dosage / Q000494:pharmacology*
D013134:Spiperone; D006220:Haloperidol; D011188:Potassium; D002746:Chlorpromazine; D004298:Dopamine