CLEARANCE OF EXOGENOUS DOPAMINE IN RAT DORSAL STRIATUM AND NUCLEUS-ACCUMBENS - ROLE OF METABOLISM AND EFFECTS OF LOCALLY APPLIED UPTAKE INHIBITORS

被引:160
作者
CASS, WA
ZAHNISER, NR
FLACH, KA
GERHARDT, GA
机构
[1] UNIV COLORADO,HLTH SCI CTR,DEPT PSYCHIAT,DENVER,CO 80262
[2] UNIV COLORADO,HLTH SCI CTR,NEUROSCI TRAINING PROGRAM,DENVER,CO 80262
[3] UNIV COLORADO,DEPT AEROSP ENGN,BOULDER,CO 80309
[4] UNIV COLORADO,HLTH SCI CTR,ROCKY MT CTR SENSOR TECHNOL,DENVER,CO 80262
关键词
COCAINE; NOMIFENSINE; DOPAMINE UPTAKE; STRIATUM; NUCLEUS ACCUMBENS; IN-VIVO ELECTROCHEMISTRY;
D O I
10.1111/j.1471-4159.1993.tb07469.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In vivo electrochemistry was used to investigate the mechanisms contributing to the clearance of locally applied dopamine in the dorsal striatum and nucleus accumbens of urethane-anesthetized rats. Chronoamperometric recordings were continuously made at 5 Hz using Nation-coated carbon fiber electrodes. When a finite amount of dopamine was pressure-ejected at 5-min intervals from a micropipette adjacent to the electrode, transient and reproducible dopamine signals were detected. Substitution of L-alpha-methyldopamine, a substrate for the dopamine transporter but not for monoamine oxidase, for dopamine in the micropipette did not substantially alter the time course of the resulting signals. This indicates that metabolism of locally applied dopamine to 3,4-dihydroxy-phenylacetic acid is not responsible for the decline in the dopamine signal. Similarly, changing the applied oxidation potential from +0.45 to +0.80 V, which allows for detection of 3-methoxytyramine formed from dopamine via catechol-0-methyltransferase, had little effect on signal amplitude or time course. In contrast, lesioning the dopamine terminals with 6-hydroxydopamine, or locally applying the dopamine uptake inhibitors cocaine or nomifensine before pressure ejection of dopamine, significantly increased the amplitude and time course of the dopamine signals in both regions. The effects of cocaine and nomifensine were greater in the nucleus accumbens than in the dorsal striatum. Local application of lidocaine and procaine had no effect on the dopamine signals. Initial attempts at modeling resulted in curves that were in qualitative agreement with our experimental findings. Taken together, these data indicate that (1) uptake of dopamine by the neuronal dopamine transporter, rather than metabolism or diffusion, is the major mechanism for clearing locally applied dopamine from the extracellular milieu of the dorsal striatum and nucleus accumbens, and (2) the nucleus accumbens is more sensitive to the effects of inhibitors of dopamine uptake than is the dorsal striatum.
引用
收藏
页码:2269 / 2278
页数:10
相关论文
共 61 条
[1]   NOMIFENSINE - REVIEW OF ITS PHARMACOLOGICAL PROPERTIES AND THERAPEUTIC EFFICACY IN DEPRESSIVE-ILLNESS [J].
BROGDEN, RN ;
HEEL, RC ;
SPEIGHT, TM ;
AVERY, GS .
DRUGS, 1979, 18 (01) :1-24
[2]   AMPHETAMINE, COCAINE, PHENCYCLIDINE AND NOMIFENSINE INCREASE EXTRACELLULAR DOPAMINE CONCENTRATIONS PREFERENTIALLY IN THE NUCLEUS ACCUMBENS OF FREELY MOVING RATS [J].
CARBONI, E ;
IMPERATO, A ;
PEREZZANI, L ;
DICHIARA, G .
NEUROSCIENCE, 1989, 28 (03) :653-661
[3]   DIFFERENCES IN DOPAMINE CLEARANCE AND DIFFUSION IN RAT STRIATUM AND NUCLEUS-ACCUMBENS FOLLOWING SYSTEMIC COCAINE ADMINISTRATION [J].
CASS, WA ;
GERHARDT, GA ;
MAYFIELD, RD ;
CURELLA, P ;
ZAHNISER, NR .
JOURNAL OF NEUROCHEMISTRY, 1992, 59 (01) :259-266
[4]   REDUCED CLEARANCE OF EXOGENOUS DOPAMINE IN RAT NUCLEUS-ACCUMBENS, BUT NOT IN DORSAL STRIATUM, FOLLOWING COCAINE CHALLENGE IN RATS WITHDRAWN FROM REPEATED COCAINE ADMINISTRATION [J].
CASS, WA ;
GERHARDT, GA ;
GILLESPIE, K ;
CURELLA, P ;
MAYFIELD, RD ;
ZAHNISER, NR .
JOURNAL OF NEUROCHEMISTRY, 1993, 61 (01) :273-283
[5]   REGIONAL DIFFERENCES IN THE REGULATION OF DOPAMINE AND NORADRENALINE RELEASE IN MEDIAL FRONTAL-CORTEX, NUCLEUS-ACCUMBENS AND CAUDATE-PUTAMEN - A MICRODIALYSIS STUDY IN THE RAT [J].
CENCI, MA ;
KALEN, P ;
MANDEL, RJ ;
BJORKLUND, A .
BRAIN RESEARCH, 1992, 581 (02) :217-228
[6]   EXTRACELLULAR DOPAMINE IN RAT STRIATUM FOLLOWING UPTAKE INHIBITION BY COCAINE, NOMIFENSINE AND BENZTROPINE [J].
CHURCH, WH ;
JUSTICE, JB ;
BYRD, LD .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1987, 139 (03) :345-348
[7]  
COSTALL B, 1977, ADV BEHAV BIOL, V21, P47
[8]  
Crank J., 1979, MATH DIFFUSION, V2nd
[9]   FORMATION AND CLEARANCE OF INTERSTITIAL METABOLITES OF DOPAMINE AND SEROTONIN IN THE RAT STRIATUM - AN INVIVO MICRODIALYSIS STUDY [J].
CUMMING, P ;
BROWN, E ;
DAMSMA, G ;
FIBIGER, H .
JOURNAL OF NEUROCHEMISTRY, 1992, 59 (05) :1905-1914
[10]   BINDING CHARACTERISTICS OF THE DOPAMINE UPTAKE INHIBITOR [H-3] NOMIFENSINE TO STRIATAL MEMBRANES [J].
DUBOCOVICH, ML ;
ZAHNISER, NR .
BIOCHEMICAL PHARMACOLOGY, 1985, 34 (08) :1137-1144