Distinct pharmacological regulation of evoked dopamine efflux in the amygdala and striatum of the rat in vivo

Garris, PA; Rm, Wightman

doi:10.1002/syn.890200311

Cited by 63 publications

(53 citation statements)

References 66 publications

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“…4). This opposes with well established effects of cocaine in the caudate and nucleus accumbens, where it increases peak dopamine release (Stamford et al, 1988;Garris and Wightman, 1995;Wu et al, 2001;Greco and Garris, 2003;Walker et al, 2006).…”

Section: Resultscontrasting

confidence: 69%

Site-Specific Role of Catechol-O-Methyltransferase in Dopamine Overflow within Prefrontal Cortex and Dorsal Striatum

Yavich¹,

Forsberg²,

Karayiorgou³

et al. 2007

J. Neurosci.

247

205

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Accumulating evidence from clinical and preclinical studies shows that catechol-O-methyltransferase (COMT) plays a significant role in dopamine metabolism in the prefrontal cortex, but not in the striatum. However, to what extent dopamine overflow in the prefrontal cortex and striatum is controlled by enzymatic degradation versus reuptake is unknown. We used COMT deficient mice to investigate the role of COMT in these two brain regions with in vivo voltammetry. A real-time analysis of evoked dopamine overflow showed that removal of dopamine was twofold slower in the prefrontal cortex of mice lacking COMT than in wild-type mice, indicating that half of the dopamine decline in this brain region results from COMT-mediated enzymatic degradation. Lack of COMT did not influence dopamine overflow/decline in the dorsal striatum. COMT-deficient mice demonstrated a small (20 -25%) but consistent increase in evoked dopamine release in the prefrontal cortex, but not in the dorsal striatum. Cocaine affected equally dopaminergic neurotransmission in the prefrontal cortex in both genotypes by prolonging 3-4 times dopamine elimination from extracellular space. Paradoxically, this happened without increase of the peak levels of evoked dopamine release. The present findings represent the first demonstration of the significant contribution of COMT in modulating the dynamics of dopamine overflow in the prefrontal cortex and underscore the therapeutic potential of manipulating COMT activity to alter dopaminergic neurotransmission in the prefrontal cortex.

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Section: Resultscontrasting

confidence: 69%

Site-Specific Role of Catechol-O-Methyltransferase in Dopamine Overflow within Prefrontal Cortex and Dorsal Striatum

Yavich¹,

Forsberg²,

Karayiorgou³

et al. 2007

J. Neurosci.

247

205

View full text Add to dashboard Cite

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“…This hypothesis is supported by the differential effects of cocaine in the medial versus the lateral striatum (Cline et al, 1995) and recent work in the nonhuman primate (Bradberry et al, 2000;Cragg et al, 2000). However, DA uptake rates in the amygdala and cortex are slower than those in the striatum Jones et al, 1995b); yet cocaine-induced increases in extracellular DA are less (Moghaddam and Bunney, 1989;Garris and Wightman, 1995a;Hurd et al, 1997), suggesting that other factors are involved.…”

mentioning

confidence: 88%

“…Interestingly, the reduced effectiveness of cocaine to increase extracellular DA in the amygdala and prefrontal cortex (Moghaddam and Bunney, 1989;Garris and Wightman, 1995a;Hurd et al, 1997) is associated with unusually slow rates for DA uptake and high rates for DA release, respectively Jones et al, 1995b). Systemic administration of cocaine has also been shown to increase extracellular DA to a greater extent in the NAc shell compared with the core (Pontieri et al, 1995;David et al, 1998).…”

Section: Preferential Effects Of Cocaine On Accumbal Damentioning

confidence: 99%

Preferential Increases in Nucleus Accumbens Dopamine after Systemic Cocaine Administration Are Caused by Unique Characteristics of Dopamine Neurotransmission

et al. 2001

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In vivo voltammetry was used to investigate the preferential increase of extracellular dopamine in the nucleus accumbens relative to the caudate-putamen after systemic cocaine administration. In the first part of this study, cocaine (40 mg/kg, i.p.) was compared with two other blockers of dopamine uptake, nomifensine (10 mg/kg, i.p.) and 3␤-( p-chlorophenyl)tropan-2␤-carboxylic acid p-isothiocyanatophenylmethyl ester hydrochloride (RTI-76; 100 nmol, i.c.v.), to assess whether the inhibitory mechanism of cocaine differed in the two regions. All three drugs robustly increased electrically evoked levels of dopamine, and cocaine elevated dopamine signals to a greater extent in the nucleus accumbens. However, kinetic analysis of the evoked dopamine signals indicated that cocaine and nomifensine increased the K m for dopamine uptake whereas the dominant effect of RTI-76 was a decrease in V max . Under the present in vivo conditions, therefore, cocaine is a competitive inhibitor of dopamine uptake in both the nucleus accumbens and caudate-putamen. Whether the preferential effect of cocaine was mediated by regional differences in the presynaptic control of extracellular DA that are described by rates for DA uptake and release was examined next by a correlation analysis. The lower rates for dopamine release and uptake measured in the nucleus accumbens were found to underlie the preferential increase in extracellular dopamine after cocaine. This relationship explains the paradox that cocaine more effectively increases accumbal dopamine despite identical effects on the dopamine transporter in the two regions. The mechanism proposed for the preferential actions of cocaine may also mediate the differential effects of psychostimulant in extrastriatal regions and other uptake inhibitors in the striatum.

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“…The order of action of these enzymes may vary according to the location of DA, because monoamine oxidase is present in presynaptic terminals (Trendelenburg et at., 1987), whereas COMT is primarily extraneuronat (Gutdberg and Marsden, 1975). In the brain, these enzymes contribute tittle to the removal of DA from the dopaminergic synapse, which is accomptished primarily by DA transporter-mediated uptake (van Home et al, 1992;Cass et al, 1993;Garns and Wightman, 1995). In A powerful technique to probe the function of a protein is to isolate it from closely retated proteins by heterologous expression of its coding DNA in celt tines that do not endogenousty express the protein.…”

Section: Introductionmentioning

confidence: 99%

Metabolism of Catecholamines by Catechol‐O‐Methyltransferase in Cells Expressing Recombinant Catecholamine Transporters

Eshleman

Stewart

Evenson

et al. 1997

Journal of Neurochemistry

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Abstract:To determine if catechol-O-methyltransferase (COMT) metabolizes catecholamines within cell lines used for heterologous expression of plasmalemmal transporters and alters the measured characteristics of 3H-substrate transport, the uptake of monoamine transporter substrates was assessed in three cell lines (C6 glioma, L-M fibroblast, and HEK293 cells) that had been transfected with the recombinant human transporters. Uptake and cellular retention of 3H-catecholamines was increased by up to fourfold by two COMT inhibitors, tropolone and Ro 41-0960, with potencies similar to those for inhibition of COMT activity, whereas the uptake of two transporter substrates that are not substrates for COMT, [3H]serotoninand [3H]MPP~, was unaffected. Direct measurement of monoamine substrates by HPLC confirmed that tropolone (1 mM) increased the retention of the catecholamines dopamine and norepinephrine, but not the retention of serotonin in HEK293 cells. Saturation analysis of the uptake of [3H]dopamineby C6 cells expressing the dopamine transporter demonstrated that tropolone (1 mM)decreased the apparent Km of transport from 0.61 biM to 0.34~iMwithout significantly altering the maximal velocity of transport. These data suggest that endogenous COMT activity in mammalian cells may alter neurotransmitter deposition and thus the apparent kinetic characteristics of transport. Key Words: Dopamine transporter -cDNA -Catechol -O -methyltransferase-Tropolone. J. Neurochem. 69, 1459-1466 (1997).We (Eshleman et al., 1994(Eshleman et al., , 1995 and others (Kitty et al., 1991;Shimada et at., 1991;Giros et at., 1992;Pristupa et al., 1994; Watt et at., 1995) have ctoned and expressed the dopamine (DA) transporter in several cell lines for the purposes of characterizing transporter-mediated uptake and release of DA, and differentiating between the interactions of abused and therapeutic drugs with the DA transporter. The issue of the appropriate cettutar environment for expression of the DA transporter is particutarty retevant because of the observation that DA is apparently taken up tess avidly by the recombinant DA transporter (Km

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Distinct pharmacological regulation of evoked dopamine efflux in the amygdala and striatum of the rat in vivo

Cited by 63 publications

References 66 publications

Site-Specific Role of Catechol-O-Methyltransferase in Dopamine Overflow within Prefrontal Cortex and Dorsal Striatum

Site-Specific Role of Catechol-O-Methyltransferase in Dopamine Overflow within Prefrontal Cortex and Dorsal Striatum

Preferential Increases in Nucleus Accumbens Dopamine after Systemic Cocaine Administration Are Caused by Unique Characteristics of Dopamine Neurotransmission

Metabolism of Catecholamines by Catechol‐O‐Methyltransferase in Cells Expressing Recombinant Catecholamine Transporters

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