Modulation of neurotransmitter release by presynaptic autoreceptors

Starke, Klaus; Göthert, M.; Kilbinger, H.

doi:10.1152/physrev.1989.69.3.864

Cited by 882 publications

(468 citation statements)

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“…Haloperidol increases electrically stimulated dopamine signals by blocking presynaptic autoreceptors that inhibit dopamine release and stimulate uptake (Meiergerd et al, 1993;Roth, 1987, 1990;Starke et al, 1989;Cass and Gerhardt, 1994;Wu et al, 2002). These mechanisms play a primary role in the increased basal extracellular dopamine levels that result from D 2 antagonist administration (Imperato and Di Chiara, 1985).…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Neurochemical Effects of Dopaminergic Drugs in Rat Striatum

Walker

Ray

Kuhn

2005

Neuropsychopharmacol

121

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: Discussionmentioning

confidence: 99%

Sex Differences in Neurochemical Effects of Dopaminergic Drugs in Rat Striatum

Walker

Ray

Kuhn

2005

Neuropsychopharmacol

121

106

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“…Maternal effect in Fragile X syndrome B Zupan and M Toth Starke et al, 1989;Usiello et al, 2000). These experiments indicated that the D2 receptor or its coupling/signaling may be the molecular target of the maternal effect.…”

Section: Introductionmentioning

confidence: 92%

“…Since the D2/3 receptor agonist quinpirole, at concentrations of 0.05-0.2 mg/kg, inhibits locomotor activity primarily via D2 autoreceptor-mediated inhibition of DA release in rodents (Cory-Slechta et al, 1996;Starke et al, 1989;Usiello et al, 2000), we could directly probe D2 autoreceptor function in H4WT mice. Since data displayed in Figure 1 showed that the maternal effect becomes apparent during the 20-60 min period in the locomotor test, drug was administered at 20 min and behavior was recorded between 40 and 60 min in Maternal effect in Fragile X syndrome B Zupan and M Toth these experiments (Figure 3a).…”

Section: Wild-type Offspring Of H Mothers Have Altered D2 Receptor Fumentioning

confidence: 99%

Wild-Type Male Offspring of fmr-1+/− Mothers Exhibit Characteristics of the Fragile X Phenotype

Zupan

Tóth

2008

Neuropsychopharmacol

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Fragile X syndrome is an X-linked disorder caused by the inactivation of the FMR-1 gene with symptoms ranging from impaired cognitive functions to seizures, anxiety, sensory abnormalities, and hyperactivity. Males are more severely affected than heterozygote (H) females, who, as carriers, have a 50% chance of transmitting the mutated allele in each pregnancy. fmr-1 knockout (KO) mice reproduce fragile X symptoms, including hyperactivity, seizures, and abnormal sensory processing. In contrast to the expectation that wild-type (WT) males born to H (fmr-1 + /À ) mothers (H4WT) are behaviorally normal and indistinguishable from WT males born to WT mothers (WT4WT); here, we show that H4WT offspring are more active than WT4WT offspring and that their hyperactivity is similar to male KO mice born to H or KO (fmr-1 À/À ) mothers (H4KO/KO4KO). H4WT mice, however, do not exhibit seizures or abnormal sensory processing. Consistent with their hyperactivity, the effect of the D2 agonist quinpirole is reduced in H4WT as well as in H4KO and KO4KO mice compared to WT4WT offspring, suggesting a diminished feedback inhibition of dopamine release. Our data indicate that some aspects of hyperactivity and associated dopaminergic changes in 'fragile X' mice are a maternal fmr-1 genotype rather than an offspring fmr-1 genotype effect.

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“…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).…”

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confidence: 99%

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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Modulation of neurotransmitter release by presynaptic autoreceptors

Cited by 882 publications

References 0 publications

Sex Differences in Neurochemical Effects of Dopaminergic Drugs in Rat Striatum

Sex Differences in Neurochemical Effects of Dopaminergic Drugs in Rat Striatum

Wild-Type Male Offspring of fmr-1+/− Mothers Exhibit Characteristics of the Fragile X Phenotype

Restricted Diffusion of Dopamine in the Rat Dorsal Striatum

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