scholarly journals Repeated treatment with cocaine or methamphetamine increases CRF2 and decreases astrocytic markers in the ventral tegmental area and substantia nigra

2019 ◽  
Author(s):  
Amanda L. Sharpe ◽  
Marta Trzeciak ◽  
Phillip Douglas ◽  
Michael J. Beckstead
Keyword(s):  
Substantia Nigra ◽  
Ventral Tegmental Area ◽  
Glutamate Transporter ◽  
Dopamine Neurons ◽  
Repeated Treatment ◽  
Glial Glutamate Transporter ◽  
Seeking Behavior ◽  
Membrane Bound ◽  
Ventral Tegmental ◽  
Abused Drugs

AbstractDopamine neurons in the substantia nigra (SN) and ventral tegmental area (VTA) play a crucial role in the reinforcing properties of abused drugs including methamphetamine and cocaine. Evidence also suggests the involvement of non-dopaminergic transmitters, including glutamate and the stress-related peptide corticotropin-releasing factor (CRF), on the chronic effects of psychostimulants in the SN/VTA. Astrocytes express a variety of membrane-bound neurotransmitter receptors and transporters which influence neurotransmission in the SN/VTA. CRF2 activity in the VTA is important for stress-induced relapse and drug-seeking behavior, but the localization of its effects are not completely understood. Here we used immunofluorescence to identify the effect of methamphetamine and cocaine administration on astrocytes, the glial glutamate transporter GLAST, and CRF2 in the SN/VTA. We treated adult male mice with i.p. injections of methamphetamine (3 mg/kg), cocaine (10 mg/kg), or saline for 12 days. Coronal brain sections were processed for immunofluorescence using S100β (marker for astrocytes), glial-specific glutamate/aspartate transporters (GLAST), and CRF2. The results showed a significant decrease in GLAST immunofluorescence in brains of mice treated with cocaine or methamphetamine compared to saline. In addition, we observed increased labelling of CRF2 in drug treated groups, a decrease in the number of S100β positive cells, and an increase in co-staining of these two markers. Our results suggest that administration of either methamphetamine or cocaine decreases astrocytic markers and increases immunoreactivity for CRF2 in the VTA, an effect that is most pronounced in S100β positive cells.

The Evolving Understanding of Dopamine Neurons in the Substantia Nigra and Ventral Tegmental Area

2018 ◽  
Vol 80 (1) ◽  
pp. 219-241 ◽  
Author(s):  
Stephanie C. Gantz ◽  
Christopher P. Ford ◽  
Hitoshi Morikawa ◽  
John T. Williams
Keyword(s):  
Substantia Nigra ◽  
Ventral Tegmental Area ◽  
Dopamine Neurons ◽  
Ventral Tegmental

Differential Modulation by Nicotine of Substantia Nigra Versus Ventral Tegmental Area Dopamine Neurons

2007 ◽  
Vol 98 (6) ◽  
pp. 3388-3396 ◽  
Author(s):  
J. Russel Keath ◽  
Michael P. Iacoviello ◽  
Lindy E. Barrett ◽  
Huibert D. Mansvelder ◽  
Daniel S. McGehee
Keyword(s):  
Substantia Nigra ◽  
Ventral Tegmental Area ◽  
Dorsal Striatum ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Synaptic Modulation ◽  
Afferent Projections ◽  
Ventral Tegmental ◽  
Midbrain Dopamine ◽  
Da Release

Midbrain dopamine (DA) neurons are found in two nuclei, the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). The SNc dopaminergic projections to the dorsal striatum are involved in voluntary movement and habit learning, whereas the VTA projections to the ventral striatum contribute to reward and motivation. Nicotine induces profound DA release from VTA dopamine neurons but substantially less from the SNc. Nicotinic acetylcholine receptor (nAChR) expression differs between these nuclei, but it is unknown whether there are differences in nAChR expression on the afferent projections to these nuclei. Here we have compared the nicotinic modulation of excitatory and inhibitory synaptic inputs to VTA and SNc dopamine neurons. Although nicotine enhances both the excitatory and inhibitory drive to SNc DA cells with response magnitudes similar to those seen in the VTA, the prevalence of these responses in SNc is much lower. We also found that a mixture of nAChR subtypes underlies the synaptic modulation in SNc, further distinguishing this nucleus from the VTA, where α7 nAChRs enhance glutamate inputs and non-α7 receptors enhance GABA inputs. Finally, we compared the nicotine sensitivity of DA neurons in these two nuclei and found larger response magnitudes in VTA relative to SNc. Thus the observed differences in nicotine-induced DA release from VTA and SNc are likely due to differences in nAChR expression on the afferent inputs as well as on the DA neurons themselves. This may explain why nicotine has a greater effect on behaviors associated with the VTA than the SNc.

NMDA alters rotenone toxicity in rat substantia nigra zona compacta and ventral tegmental area dopamine neurons

2012 ◽  
Vol 33 (3) ◽  
pp. 429-435 ◽  
Author(s):  
Adam C. Munhall ◽  
Yan-Na Wu ◽  
John K. Belknap ◽  
Charles K. Meshul ◽  
Steven W. Johnson
Keyword(s):  
Substantia Nigra ◽  
Ventral Tegmental Area ◽  
Dopamine Neurons ◽  
Ventral Tegmental ◽  
Rat Substantia Nigra

scholarly journals Ventral Tegmental Area GABA, glutamate, and glutamate-GABA neurons are heterogenous in their electrophysiological and pharmacological properties

2020 ◽  
Author(s):  
Jorge Miranda-Barrientos ◽  
Ian Chambers ◽  
Smriti Mongia ◽  
Bing Liu ◽  
Hui-Ling Wang ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Viral Vectors ◽  
Ex Vivo ◽  
Glutamate Transporter ◽  
Receptor Activation ◽  
Firing Frequency ◽  
Dopamine Neurons ◽  
Gaba Neurons ◽  
Double Transgenic Mouse ◽  
Ventral Tegmental

AbstractThe ventral tegmental area (VTA) contains dopamine neurons intermixed with GABA-releasing (expressing vesicular GABA transporter, VGaT), glutamate-releasing (expressing vesicular glutamate transporter, VGluT2), and co-releasing (co-expressing VGaT and VGluT2) neurons. By delivering INTRSECT viral vectors into VTA of double vglut2-Cre/vgat-Flp transgenic mice, we targeted specific VTA cell populations for ex vivo recordings. We found that VGluT2+ VGaT− and VGluT2+ VGaT+ neurons on average had relatively hyperpolarized resting membrane voltage, greater rheobase, and lower spontaneous firing frequency compared to VGluT2− VGaT+ neurons, suggesting that VTA glutamate-releasing and glutamate-GABA co-releasing neurons require stronger excitatory drive to fire than GABA-releasing neurons. In addition, we detected expression of Oprm1mRNA (encoding μ opioid receptors, MOR) in VGluT2+ VGaT− and VGluT2− VGaT+ neurons, and their hyperpolarization by the MOR agonist DAMGO. Collectively, we demonstrate the utility of the double transgenic mouse to access VTA glutamate, glutamate-GABA and GABA neurons, and show some electrophysiological heterogeneity among them.Impact StatementSome physiological properties of VTA glutamate-releasing and glutamate-GABA co-releasing neurons are distinct from those of VTA GABA-releasing neurons. μ-opioid receptor activation hyperpolarizes some VTA glutamate-releasing and some GABA-releasing neurons.

Chemogenetic activation of dopamine neurons in the ventral tegmental area, but not substantia nigra, induces hyperactivity in rats

2016 ◽  
Vol 26 (11) ◽  
pp. 1784-1793 ◽  
Author(s):  
Linde Boekhoudt ◽  
Azar Omrani ◽  
Mieneke C.M. Luijendijk ◽  
Inge G. Wolterink-Donselaar ◽  
Ellen C. Wijbrans ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Ventral Tegmental Area ◽  
Dopamine Neurons ◽  
Ventral Tegmental
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