Determination of release and uptake parameters from electrically evoked dopamine dynamics measured by real-time voltammetry

Wu, Qun; Reith, Maarten E. A.; Wightman, R. Mark; Kawagoe, Kirk T.; Garris, Paul A.

doi:10.1016/s0165-0270(01)00459-9

Cited by 168 publications

(347 citation statements)

References 55 publications

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“…Non-linear curve fitting using a simplex algorithm calculated V max , K m , and [DA] p from in vivo data at each frequency from 20 to 60 Hz (Wu et al, 2001b). All three parameters were typically allowed to float in this analysis, although occasionally V max was fixed to the value determined from the slope of the clearance phase of 60 Hz 2 s overflow curves where [DA]bK m (Wu et al, 2001b).…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Neurochemical Effects of Dopaminergic Drugs in Rat Striatum

Walker

Ray

Kuhn

2005

Neuropsychopharmacol

117

103

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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: Discussionmentioning

confidence: 99%

Sex Differences in Neurochemical Effects of Dopaminergic Drugs in Rat Striatum

Walker

Ray

Kuhn

2005

Neuropsychopharmacol

117

103

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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%

“…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.…”

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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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“…When the DAT is saturated, the slope of the linear clearance profile is the apparent V max of DA uptake. 22,24,42 The apparent V max in fast domains, 3.91 ± 0.40 μM/s, is significantly larger than that in slow domains, 2.46 ± 0.14 μM/s (t test of independent samples: p < 0.0002).…”

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confidence: 94%

Restricted Diffusion of Dopamine in the Rat Dorsal Striatum

Taylor

Ilitchev

Michael

2013

ACS Chem. Neurosci.

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Recent evidence has shown that the dorsal striatum of the rat is arranged as a patchwork of domains that exhibit distinct dopamine kinetics and concentrations. This raises the pressing question of how these distinct domains are maintained, especially if dopamine is able to diffuse through the extracellular space. Diffusion between the domains would eliminate the concentration differences and, thereby, the domains themselves. The present study is a closer examination of dopamine's ability to diffuse in the extracellular space. We used voltammetry to record dopamine overflow in dorsal striatum while stimulating the medial forebrain bundle over a range of stimulus currents and frequencies. We also examined the effects of drugs that modulated the dopamine release (raclopride and quinpirole) and uptake (nomifensine). Examining the details of the temporal features of the evoked profiles reveals no clear evidence for long-distance diffusion of dopamine between fast and slow domains, even though uptake inhibition by nomifensine clearly prolongs the time that dopamine resides in the extracellular space. Our observations support the conclusion that striatal tissue has the capacity to retain dopamine molecules, thereby limiting its tendency to diffuse through the extracellular space. KEYWORDS: Dopamine, dopamine transporter, diffusion, evoked release, voltammetry, dorsal striatum C entral dopamine (DA) systems participate in numerous aspects of brain function, 1,2 and their dysfunction contributes to a broad array of disorders and diseases including Parkinson's disease, 3 schizophrenia, 4 and attention deficit hyperactivity disorder. 5 Broadly speaking, the physiological function of the DA molecules themselves is to bind to post-and presynaptic receptors to modulate the activity of the postsynaptic targets 6 and to self-regulate DAergic activity, 7 respectively. Consequently, numerous drugs act by modulating extracellular DA concentrations (e.g., L-DOPA, MAO inhibitors, and inhibitors of the dopamine transporter (DAT) 8−11 ) or by modulating or mimicking the binding of DA to its receptors (DA agonists and antagonists). 12,13 Some of the drugs that target DA systems have important therapeutic applications 14,15 while others have high potential for illicit abuse: 16−18 some therapeutic drugs are also abused. 19 Thus, it is significant to know the extracellular DA concentration per se, to know the kinetics of DA release and clearance that determine the concentration, and to know the actions of drugs that target DA systems.Recently, we have demonstrated that the DA terminal field in the rat dorsal striatum contains a patchwork of kinetic spatial domains. The fast and slow domains were brought to light by recordings of extracellular DA with fast-scan cyclic voltammetry (FSCV) at carbon fiber microelectrodes during electrical stimulation of the medial forebrain bundle (MFB). The extracellular concentration of DA, the kinetics of DA release and clearance, the short-term plasticity of DA release, and the actions of DA-ta...

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Determination of release and uptake parameters from electrically evoked dopamine dynamics measured by real-time voltammetry

Cited by 168 publications

References 55 publications

Sex Differences in Neurochemical Effects of Dopaminergic Drugs in Rat Striatum

Sex Differences in Neurochemical Effects of Dopaminergic Drugs in Rat Striatum

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

Restricted Diffusion of Dopamine in the Rat Dorsal Striatum

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