HALOPERIDOL AND CLOZAPINE INCREASE INTRANEURONAL DOPAMINE METABOLISM, BUT NOT GAMMA-BUTYROLACTONE-RESISTANT DOPAMINE RELEASE

被引:5
作者
CHRAPUSTA, SJ
KAROUM, F
EGAN, MF
WYATT, RJ
机构
[1] Neuropsychiatry Branch, NIMH Neuroscience Center at Saint Elizabeths, Washington
关键词
NEUROLEPTICS; DOPAMINE RELEASE; DOPAMINE METABOLISM; 3-METHOXYTYRAMINE; STRIATUM; NUCLEUS ACCUMBENS; FRONTAL CORTEX; DEPOLARIZATION BLOCK; (RAT);
D O I
10.1016/0014-2999(93)90359-P
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In a previous study, two coexisting mechanisms of dopamine release were identified in dopamine neuron terminals. One can be blocked with gamma-butyrolactone, suggesting it is impulse flow-dependent, while the other one cannot and is apparently impulse flow-independent. The goal of this study was to further characterize the gamma-butyrolactone-resistant mechanism and its relation to dopamine metabolism. Following acute and chronic haloperidol or clozapine treatment, gamma-butyrolactone was given to block dopamine neuronal impulse flow. In all groups, 3-methoxytyramine levels after monoamine oxidase inhibition with pargyline (an index of dopamine release) were measured in the frontal cortex, nucleus accumbens and striatum. Regional steady-state levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were also measured in the rats treated acutely with neuroleptics. In all three regions, gamma-butyrolactone reduced the 3-methoxytyramine levels by over 50% after chronic neuroleptic treatment. This indicates that dopamine release from the terminals is primarily impulse flow-dependent during chronic neuroleptic treatment, both in the dopamine neurons which do undergo depolarization block, and in those that do not. No neuroleptic effect on the gamma-butyrolactone-resistant dopamine release was observed, while DOPAC and HVA were markedly elevated by the acute treatment, suggesting a predominant production of these metabolites from unreleased dopamine.
引用
收藏
页码:135 / 142
页数:8
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