المؤلفون: Bass, Caroline E., Grinevich, Valentina P., Gioia, Dominic, Day-Brown, Jonathan D., Bonin, Keith D., Stuber, Garret D., Weiner, Jeff L., Budygin, Evgeny A.

المصدر: Frontiers in Behavioral Neuroscience; Nov2013, Vol. 7, p1-10, 10p

مصطلحات موضوعية: DOPAMINERGIC neurons, ETHANOL, GENETIC engineering, DOPAMINE, OPSINS

مستخلص: There is compelling evidence that acute ethanol exposure stimulates ventral tegmental area (VTA) dopamine cell activity and that VTA-dependent dopamine release in terminal fields within the nucleus accumbens plays an integral role in the regulation of ethanol drinking behaviors. Unfortunately, due to technical limitations, the specific temporal dynamics linking VTA dopamine cell activation and ethanol self-administration are not known. In fact, establishing a causal link between specific patterns of dopamine transmission and ethanol drinking behaviors has proven elusive. Here, we sought to address these gaps in our knowledge using a newly developed viral-mediated gene delivery strategy to selectively express Channelrhodopsin-2 (ChR2) on dopamine cells in the VTA of wild-type rats. We then used this approach to precisely control VTA dopamine transmission during voluntary ethanol drinking sessions. The results confirmed that ChR2 was selectively expressed on VTA dopamine cells and delivery of blue light pulses to the VTA induced dopamine release in accumbal terminal fields with very high temporal and spatial precision. Brief high frequency VTA stimulation induced phasic patterns of dopamine release in the nucleus accumbens. Lower frequency stimulation, applied for longer periods mimicked tonic increases in accumbal dopamine. Notably, using this optogenetic approach in rats engaged in an intermittent ethanol drinking procedure, we found that tonic, but not phasic, stimulation of VTA dopamine cells selectively attenuated ethanol drinking behaviors. Collectively, these data demonstrate the effectiveness of a novel viral targeting strategy that can be used to restrict opsin expression to dopamine cells in standard outbred animals and provide the first causal evidence demonstrating that tonic activation of VTA dopamine neurons selectively decreases ethanol self-administration behaviors. [ABSTRACT FROM AUTHOR]

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المؤلفون: Deal, Alex L.¹ (AUTHOR), Bass, Caroline E.² (AUTHOR), Grinevich, Valentina P.¹ (AUTHOR), Delbono, Osvaldo³ (AUTHOR), Bonin, Keith D.⁴ (AUTHOR), Weiner, Jeff L.⁵ (AUTHOR), Budygin, Evgeny A.¹ (AUTHOR) ebudygin@wakehealth.edu

المصدر: Neuroscience. Sep2020, Vol. 443, p84-92. 9p.

مصطلحات موضوعية: *LOCUS coeruleus, *ALCOHOL drinking, *BEHAVIOR

مستخلص: • Alcohol-drinking behaviors can be controlled through LC optostimulation. • Tonic stimulation during a drinking session results in increased alcohol intake. • Phasic stimulation during a drinking session results in decreased alcohol intake. • Tonic stimulation during an extinction trial does not alter alcohol-seeking behavior. • Phasic stimulation during an extinction trial suppresses alcohol-seeking behavior. The relationship between stress and alcohol-drinking behaviors has been intensively explored; however, neuronal substrates and neurotransmitter dynamics responsible for a causal link between these conditions are still unclear. Here, we optogenetically manipulated locus coeruleus (LC) norepinephrine (NE) activity by applying distinct stimulation protocols in order to explore how phasic and tonic NE release dynamics control alcohol-drinking behaviors. Our results clearly demonstrate contrasting behavioral consequences of LC-NE circuitry activation during low and high frequency stimulation. Specifically, applying tonic stimulation during a standard operant drinking session resulted in increased intake, while phasic stimulation decreased this measure. Furthermore, stimulation during extinction probe trials, when the lever press response was not reinforced, did not significantly alter alcohol-seeking behavior if a tonic pattern was applied. However, phasic stimulation substantially suppressed the number of lever presses, indicating decreased alcohol seeking under the same experimental condition. Given the well-established correlative link between stress and increased alcohol consumption, here we provide the first evidence that tonic LC-NE activity plays a causal role in stress-associated increases in drinking. [ABSTRACT FROM AUTHOR]

المؤلفون: Mikhailova, Maria A.^1,2, Bass, Caroline E.³, Grinevich, Valentina P.¹, Chappell, Ann M.⁴, Deal, Alex L.¹, Bonin, Keith D.⁵, Weiner, Jeff L.⁴, Gainetdinov, Raul R.², Budygin, Evgeny A.^1,2 ebudygin@wakehealth.edu

المصدر: Neuroscience. Oct2016, Vol. 333, p54-64. 11p.

مصطلحات موضوعية: *OPTOGENETICS, *DOPAMINERGIC neurons, *NUCLEUS accumbens, *CELLULAR signal transduction, *SUCROSE

مستخلص: Recent optogenetic studies demonstrated that phasic dopamine release in the nucleus accumbens may play a causal role in multiple aspects of natural and drug reward-related behaviors. The role of tonic dopamine release in reward consummatory behavior remains unclear. The current study used a combinatorial viral-mediated gene delivery approach to express ChR2 on mesolimbic dopamine neurons in rats. We used optical activation of this dopamine circuit to mimic tonic dopamine release in the nucleus accumbens and to explore the causal relationship between this form of dopamine signaling within the ventral tegmental area (VTA)-nucleus accumbens projection and consumption of a natural reward. Using a two bottle choice paradigm (sucrose vs. water), the experiments revealed that tonic optogenetic stimulation of mesolimbic dopamine transmission significantly decreased reward consummatory behaviors. Specifically, there was a significant decrease in the number of bouts, licks and amount of sucrose obtained during the drinking session. Notably, activation of VTA dopamine cell bodies or dopamine terminals in the nucleus accumbens resulted in identical behavioral consequences. No changes in water intake were evident under the same experimental conditions. Collectively, these data demonstrate that tonic optogenetic stimulation of VTA-nucleus accumbens dopamine release is sufficient to inhibit reward consummatory behavior, possibly by preventing this circuit from engaging in phasic activity that is thought to be essential for reward-based behaviors. [ABSTRACT FROM AUTHOR]

المؤلفون: Bass, Caroline E.¹, Grinevich, Valentina P.², Kulikova, Alexandra D.², Bonin, Keith D.³, Budygin, Evgeny A.² ebudygin@wakehealth.edu

المصدر: Journal of Neuroscience Methods. Apr2013, Vol. 214 Issue 2, p149-155. 7p.

مصطلحات موضوعية: *DOPAMINE, *CYCLIC voltammetry, *SUBSTANTIA nigra, *TISSUES, *BRAIN stimulation, *LABORATORY rats

مستخلص: Abstract: In this study, the first in-depth analysis of optically induced dopamine release using fast-scan cyclic voltammetry on striatal slices from rat brain was performed. An adeno-associated virus that expresses Channelrhodopsin-2 was injected in the substantia nigra. Tissue was collected and sectioned into 400μm-thick coronal slices 4 weeks later. Blue laser light (473nm) was delivered through a fiber optic inserted into slice tissue. Experiments revealed some difference between maximal amplitudes measured from optically and electrically evoked dopamine effluxes. Specifically, there was an increase in the amplitude of dopamine release induced by electrical stimulation in comparison with light stimulations. However, we found that dopamine release is more sensitive to changes in the pulse width in the case of optical stimulation. Light-stimulated dopamine was increased as the stimulation pulse widened. There was no difference with repeated stimulations at five minute intervals between stimulation sources and dopamine signal was stable during recording sessions, while one minute intervals resulted in a decline in the amplitude from both sources. Optical stimulation can also produce an artifact that is distinguishable from dopamine by the cyclic voltammogram. These results confirm that optical stimulation of dopamine is a sound approach for future pharmacological studies in slices. [Copyright &y& Elsevier]