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

Wu, Qun; Reith, Maarten E. A.; Kuhar, Michael J.; Carroll, F. Ivy; Garris, Paul A.

doi:10.1523/jneurosci.21-16-06338.2001

Cited by 117 publications

(161 citation statements)

References 47 publications

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“…The greater increase in dopamine after cocaine in females is consistent with the theoretical simulations of Wu et al (2001a) which show that cocaine should induce greatest percent increases in dopamine efflux in regions where release rates are lower and uptake rates are higher. Analysis of present baseline data from the cocaine-treated rats indicated that V max was 93% higher in females than in males, and [DA] p was 65% higher in females.…”

Section: Discussionsupporting

confidence: 85%

Sex Differences in Neurochemical Effects of Dopaminergic Drugs in Rat Striatum

Walker

Ray

Kuhn

2005

Neuropsychopharmacol

120

106

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Previous data indicate that dopamine neurotransmission is differently regulated in male and female rats. The purpose of the present study was to investigate the dopamine transporter and autoreceptor as potential loci responsible for this sex difference. Fast cyclic voltammetry at carbon-fiber microelectrodes was used to monitor changes in electrically evoked levels of extracellular dopamine in the striata of anesthetized male and female rats before and after administration of an uptake inhibitor, a dopamine D 2 antagonist, or a D 3 /D 2 agonist. Administration of 40 mg/kg cocaine ip increased electrically-evoked extracellular dopamine concentrations in both sexes, but to a significantly greater extent in female striatum at the higher stimulation frequencies. The typical antipsychotic, haloperidol, increased dopamine efflux in both sexes but the effect was twice as large in the female striatum. The D 3 /D 2 agonist quinpirole induced an unexpected, transient increase in dopamine efflux following high-frequency stimulation only in females, and evoked dopamine was higher in females across this entire time course. More detailed analysis of cocaine effects revealed no fundamental sex differences in the interaction of cocaine with DAT in vivo or in synaptosomes. These results indicate that nigrostriatal dopamine neurotransmission in the female rat is more tightly regulated by autoreceptor and transporter mechanisms, perhaps related by greater autoreceptor control of DAT activity. Thus, baseline sex differences in striatal dopamine regulation induce different pharmacologic responses. These results contribute to understanding sex differences in stimulant-induced locomotor activity in rats and may have broader implications for neurologic disorders and their pharmacotherapies in humans.

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Section: Discussionsupporting

confidence: 85%

Sex Differences in Neurochemical Effects of Dopaminergic Drugs in Rat Striatum

Walker

Ray

Kuhn

2005

Neuropsychopharmacol

120

106

View full text Add to dashboard Cite

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“…Animal studies suggest that this reflects regional differences in drug-induced increases in synaptic DA levels (Di Chiara and Imperato, 1988) rather than an artifact of the PET method. Mechanisms proposed to mediate this preferential effect include regional variability in DA release, and in the density and activity of DA transporters and DA cell innervation (Haber and McFarland, 1999;Wu et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Decreasing Amphetamine-Induced Dopamine Release by Acute Phenylalanine/Tyrosine Depletion: A PET/[11C]Raclopride Study in Healthy Men

Leyton

Dagher

Boileau

et al. 2003

Neuropsychopharmacol

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Acute phenylalanine/tyrosine depletion (APTD) has been proposed as a new method to decrease catecholamine neurotransmission safely, rapidly, and transiently. Validation studies in animals are encouraging, but direct evidence in human brain is lacking. In the present study, we tested the hypothesis that APTD would reduce stimulated dopamine (DA) release, as assessed by positron emission tomography (PET) and changes in [ 11 C]raclopride binding potential (BP), a measure of DA D2/D3 receptor availability. Eight healthy men received two PET scans, both following d-amphetamine, 0.3 mg/kg, p.o., an oral dose known to decrease [ 11 C]raclopride BP in ventral striatum. On the morning before each scan, subjects ingested, in counter-balanced order, an amino-acid mixture deficient in the catecholamine precursors, phenylalanine, and tyrosine, or a nutritionally balanced mixture. Brain parametric images were generated by calculating [ 11 C]raclopride BP at each voxel. BP values were extracted from the t-map (threshold: t ¼ 4.2, equivalent to po0.05, Bonferroni corrected) and a priori identified regions of interest from each individual's coregistered magnetic resonance images. Both receptor parametric mapping and region of interest analyses indicated that [ 11 C]raclopride binding was significantly different on the two test days in the ventral striatum (peak t ¼ 6.31; x ¼ À25, y ¼ À8, and z ¼ 0.1). In the t-map defined cluster, [ 11 C]raclopride BP values were 11.8 7 11.9% higher during the APTD session (po0.05). The reduction in d-amphetamine-induced DA release exhibited a linear association with the reduction in plasma tyrosine levels (r ¼ À0.82, po0.05). Together, the results provide the first direct evidence that APTD decreases stimulated DA release in human brain. APTD may be a suitable new tool for human neuropsychopharmacology research.

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“…NIH-PA Author Manuscript NIH-PA Author Manuscript which are associated with its rewarding and stimulating properties [10,18,29,30]. Using FSCV coupled with kinetic analysis, cocaine has been found to act as a competitive inhibitor of DA uptake by altering K m [10,11,[18][19][20]29,30].…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Dopamine uptake inhibition is positively correlated with cocaine-induced stereotyped behavior

Budygin¹

2007

Neuroscience Letters

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The inhibition of dopamine (DA) uptake and the increase of extracellular DA with consequent activation of DA receptors in specific brain regions such as the nucleus accumbens (NAc) and dorsal striatum are an important, but may be not an exclusive mechanism for behavioral excitation induced by psychostimulants [2,5,14,15,24,25]. A typical spectrum of acute cocaineinduced arousal effects in animal models includes locomotor activation and stereotyped behavior consisting of continuous sniffing, rearing, licking and gnawing. At low and moderate doses, cocaine preferentially enhances locomotor activity and this effect correlates with the decrease in DA clearance in the NAc of freely moving rats [24]. At high doses, the effect of cocaine on the stereotyped activity became predominant [1]. It is unknown whether a strong relationship exists between the stereotypy and cocaine-induced DA uptake changes in the NAc.In this study we have employed fast-scan cyclic voltammetry (FSCV) on freely moving rats to determine whether a correlation exists between the increase in the stereotyped behavior and DA uptake inhibition following cocaine (20 mg/kg, i.p.) administration. The FSCV was chosen since the general characteristics of this technique allow an examination of the DA uptake kinetics without DA release or metabolism contributions [1,28,30].Male Sprague-Dawley rats (300-350 g; Charles River, Raleigh, NC) were housed on a 12:12 light/dark cycle with food and water ad libitum. Rats were group housed before surgery and singly housed after surgery. All protocols were approved by the Institutional Animal Care and Use Committee at Wake Forest University. Rats were anesthetized with ketamine (100 mg/kg) and xylazine (10 mg/kg) and placed in a stereotaxic frame. A guide cannula (Bioanalytical Systems, West Lafayette, IN) was positioned above the NAc core (AP + 1.3, L+1.3, V-2.0 mm from bregma). An Ag/AgCl reference electrode was implanted in the contralateral hemisphere. A bipolar stimulating electrode was lowered to the ventral tegmental area ipsilateral to the guide cannula at 5.2 mm posterior and 1.0 mm lateral to bregma. The stimulating electrode depth was optimized to evoke DA release in the NAc (24 rectangular pulses, 60 Hz, 120 μA, 2 ms/phase, biphasic), monitored using a carbon fiber microelectrode inserted through the guide cannula. The rats were individually housed and allowed to recover for 48 hrs, then they were placed in the test chamber and a new carbon fiber electrode was inserted into the NAc core. The reference and carbon fiber electrodes were connected to a head-mounted voltammetric amplifier (UNC Electronics Design Facility, Chapel Hill, NC) attached to a swivel at the top of the test chamber. Voltammetric recordings were made at the carbon fiber electrode every 100 ms by applying a triangular waveform (-0.4 to +1.2 V, 300 V/s). Data were Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of th...

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

Cited by 117 publications

References 47 publications

Sex Differences in Neurochemical Effects of Dopaminergic Drugs in Rat Striatum

Sex Differences in Neurochemical Effects of Dopaminergic Drugs in Rat Striatum

Decreasing Amphetamine-Induced Dopamine Release by Acute Phenylalanine/Tyrosine Depletion: A PET/[11C]Raclopride Study in Healthy Men

Dopamine uptake inhibition is positively correlated with cocaine-induced stereotyped behavior

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