Fast cyclic voltammetry in rat brain slices containing the nucleus accumbens, was used to examine the regulation of the extracellular concentration of electrically stimulated dopamine overflow in the core, shell and rostral pole. One microM (-)-sulpiride, significantly increased dopamine overflow in all 3 regions but only when the duration of stimulation was greater than 500 ms. One microM cocaine, significantly potentiated dopamine overflow in all 3 regions following all patterns of stimulation. In the presence of 1 microM cocaine, superfusion with 1 microM (-)-sulpiride did not result in a further increase in dopamine overflow at any frequency of stimulation in the rostral pole, but significant increases in dopamine overflow were observed after stimulation with 20 pulses at 10 or 20 Hz in the core or shell; the degree of potentiation was greater in the shell than core. Quinpirole inhibited single pulse stimulated dopamine overflow in a concentration dependent manner (maximum inhibition (100%) in all regions) but was significantly less potent in the rostral pole than in the core or shell. Increasing the number of pulses to 2 or 4 pulses at 50 Hz resulted in a shift of the quinpirole dose-response curve to the right in all regions and in the rostral pole, a significant reduction in the maximum inhibition of dopamine overflow to both stimulation parameters. In the shell a significant reduction in maximum inhibition was only seen with 4 pulses at 50 Hz stimulation, whereas in the core there was no change in the maximum inhibitory effect of quinpirole. Neuronal uptake and D2 autoreceptor activity contribute to regulation of the extracellular concentration of dopamine in core, shell and rostral pole. The relative importance of either uptake or autoreceptor control is region and stimulus dependent.
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http://dx.doi.org/10.1016/0006-8993(95)00894-v | DOI Listing |
Pharmacol Res
January 2025
Center for Brain Research, Department of Molecular Neurosciences, Medical University Vienna, Vienna, Austria. Electronic address:
α6-containing GABA receptors (α6GABARs) are strongly expressed in cerebellar granule cells and are of central importance for cerebellar functions. The cerebellum not only is involved in regulation of motor activity, but also in regulation of thought, cognition, emotion, language, and social behavior. Activation of α6GABARs enhances the precision of sensory inputs, enables rapid and coordinated movement and adequate responses to the environment, and protects the brain from information overflow.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
State Key Laboratory of Membrane Biology, National Biomedical Imaging Center and Institute of Molecular Medicine, College of Future Technology, Peking-Tsinghua Center for Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China.
Dopamine (DA) in the striatum is vital for motor and cognitive behaviors. Midbrain dopaminergic neurons generate both tonic and phasic action potential (AP) firing patterns in behavior mice. Besides AP numbers, whether and how different AP firing patterns per se modulate DA release remain largely unknown.
View Article and Find Full Text PDFMol Neurobiol
November 2024
State Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Joint Research Center for Food Nutrition and Health of IHM, Anhui Agricultural University, Hefei, 230036, China.
Non-physiological disorders release dopamine into extracellular brain fluid to induce neurodegenerative brain diseases. The harmful mechanism of dopamine overflow is attributed to the dopamine-mediated production of hydroxyl radicals, suggesting that transition metal copper which is high in the brain is involved in promoting dopamine oxidation. MPP+ , an intermediate formed from the conversion of MPTP, is one of the most potent dopamine-releasing agents.
View Article and Find Full Text PDFFront Pharmacol
August 2024
Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, United States.
The rewarding effects of drugs of abuse are associated with the dopaminergic system in the limbic circuitry. Nicotine exposure during adolescence is linked to increased use of drugs of abuse with nicotine and methamphetamine (METH) commonly used together. Nicotine acts on neuronal nicotinic acetylcholine receptor (nAChR) systems, critical for reward processing and drug reinforcement, while METH leads to a higher dopamine (DA) efflux in brain reward regions.
View Article and Find Full Text PDFBrain Behav Immun
August 2024
School of Pharmacy, Health Science Center, Ningbo University, Ningbo 315211, China. Electronic address:
It is widely believed that the activation of the central dopamine (DA) system is crucial to the rewarding effects of methamphetamine (METH) and to the behavioral outcomes of METH use disorder. It was reported that METH exposure induced gasdermin D (GSDMD)-dependent pyroptosis in rats. The membrane pore formation caused by METH-induced pyroptosis may also contribute to the overflow of DA into the extracellular space and subsequently increase the DA levels in the brain.
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