Ventral Tegmental Area Microinjected-SKF38393 Increases Regular Chow Intake in 18 Hours Food-Deprived Rats

Introduction: Ventral Tegmental Area (VTA) dopamine neurons play an important role in reward mechanisms of food intake, and VTA dopamine receptors exist on the terminal of glutamatergic and GABAergic neurons and regulate Gamma-Aminobutyric Acid (GABA) and glutamate release. To our knowledge, no evidence indicates any role for VTA D1 dopamine receptors in regular chow intake. Methods: In this paper, different dose of SKF38393, a D1 receptor agonist, was microinjected in VTA of 18-h food deprived-conscious rats and food intake was measured. Results: Our results revealed that VTAmicroinjected SKF383993 increased regular chow intake in a dose-dependent manner. The SKF3833 stimulatory effect persisted over 2 h post-injection. The results showed that the SKF38393, at doses less than 5 μg, did not affect locomotor activities. Conclusion: VTA D1-like and/or serotonergic receptors may be involved in regulatory pathways. the current study suggests that VTA D1-like and/or serotonergic receptors not only affects food reward but is also involved in regulatory mechanisms of regular feeding.

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Serotonin Reduces the Hyperpolarization-Activated Current (Ih) in Ventral Tegmental Area Dopamine Neurons: Involvement of 5-HT2 Receptors and Protein Kinase C

Journal of Neurophysiology ◽

10.1152/jn.00281.2003 ◽

2003 ◽

Vol 90 (5) ◽

pp. 3201-3212 ◽

Cited By ~ 53

Author(s):

Zhaoping Liu ◽

E. Bradshaw Bunney ◽

Sarah B. Appel ◽

Mark S. Brodie

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Ventral Tegmental Area ◽

Kinase Inhibitor ◽

Brain Slices ◽

Dopamine Neurons ◽

Dependent Manner ◽

Cationic Current ◽

Kinase C ◽

Ventral Tegmental

Dopaminergic neurons of the ventral tegmental area (VTA) have been implicated in the rewarding properties of drugs of abuse and in the etiology of schizophrenia; serotonin modulation of these neurons may play a role in these phenomena. Whole cell patch-in-the-slice recording in rat brain slices was used to investigate modulation of the hyperpolarization-activated cationic current Ih by serotonin in these neurons. Serotonin (50-500 μM) reduced the amplitude of Ih in a concentration-dependent manner; this effect was reversible after prolonged washout of serotonin. This effect was mimicked by the 5-HT2 agonist α-methylserotonin (25 μM) and reversed by the 5-HT2 antagonist ketanserin (25 μM). Serotonin reduced the maximal Ih current and conductance (measured at -130 mV) and caused a negative shift in the voltage dependence of Ih activation. The serotonin-induced reduction in Ih amplitude was antagonized by intracellular administration of the nonspecific protein kinase inhibitor H-7 (75 μM) and the selective protein kinase C inhibitor chelerythrine (25 μM). The protein kinase C activator phorbol 12, 13 diacetate (PDA, 2 μM) reduced Ih amplitude; when PDA and serotonin were applied together, the effect on Ih was less than additive. These data support the conclusion that serotonin reduces Ih in dopaminergic VTA neurons by acting at serotonin 5-HT2 receptors, which activate protein kinase C. This reduction of Ih may be physiologically important, as the selective inhibitor of Ih, ZD7288, significantly increased dopamine inhibition of firing rate of dopaminergic VTA neurons, an effect that we previously demonstrated with serotonin.

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Morphine selectively promotes glutamate release from glutamatergic terminals of projection neurons from medial prefrontal cortex to dopamine neurons of ventral tegmental area

10.1101/133090 ◽

2017 ◽

Cited By ~ 2

Author(s):

Li Yang ◽

Ming Chen ◽

Ping Zheng

Keyword(s):

Prefrontal Cortex ◽

Locomotor Activity ◽

Ventral Tegmental Area ◽

Medial Prefrontal Cortex ◽

Lateral Hypothalamus ◽

Basolateral Amygdala ◽

Glutamate Release ◽

Dopamine Neurons ◽

Projection Neurons ◽

Ventral Tegmental

AbstractRecently, we found that morphine promoted presynaptic glutamate release of dopamine (DA) neurons in the ventral tegmental area (VTA), which constituted the main mechanism for morphine-induced increase in VTA-DA neuron firing and related behaviors (Chen et al., 2015). However, what source of presynaptic glutamate release of DA neurons in the VTA is promoted by morphine remains unknown. To address this question, we used optogenetic strategy to selectively activate glutamatergic inputs from different projection neurons and then observed the effect of morphine on them. The result shows that morphine promotes glutamate release from glutamatergic terminals of projection neurons from the medial prefrontal cortex (mPFC) to VTA DA neurons, but has no effect on that from the basolateral amygdala (BLA) or the lateral hypothalamus (LH) to VTA DA neurons, and the inhibition of glutamatergic projection neurons from the mPFC to the VTA significantly reduces morphine-induced increase in locomotor activity of mice.

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The food intake-suppressive effects of glucagon-like peptide-1 receptor signaling in the ventral tegmental area are mediated by AMPA/kainate receptors

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00413.2013 ◽

2013 ◽

Vol 305 (11) ◽

pp. E1367-E1374 ◽

Cited By ~ 87

Author(s):

Elizabeth G. Mietlicki-Baase ◽

Pavel I. Ortinski ◽

Laura E. Rupprecht ◽

Diana R. Olivos ◽

Amber L. Alhadeff ◽

...

Keyword(s):

Food Intake ◽

Ventral Tegmental Area ◽

Dopamine Neurons ◽

Kainate Receptors ◽

System Control ◽

Receptor Signaling ◽

Palatable Food ◽

Glucagon Like Peptide ◽

Ventral Tegmental ◽

Glucagon Like Peptide 1

Glucagon-like peptide-1 receptor (GLP-1R) activation in the ventral tegmental area (VTA) is physiologically relevant for the control of palatable food intake. Here, we tested whether the food intake-suppressive effects of VTA GLP-1R activation are mediated by glutamatergic signaling within the VTA. Intra-VTA injections of the GLP-1R agonist exendin-4 (Ex-4) reduced palatable high-fat food intake in rats primarily by reducing meal size; these effects were mediated in part via glutamatergic AMPA/kainate but not NMDA receptor signaling. Additional behavioral data indicated that GLP-1R expressed specifically within the VTA can partially mediate the intake- and body weight-suppressive effects of systemically administered Ex-4, offering the intriguing possibility that this receptor population may be clinically relevant for food intake control. Intra-VTA Ex-4 rapidly increased tyrosine hydroxylase levels within the VTA, suggesting that GLP-1R activation modulates VTA dopaminergic signaling. Further evidence for this hypothesis was provided by electrophysiological data showing that Ex-4 increased the frequency of AMPA-mediated currents and reduced the paired/pulse ratio in VTA dopamine neurons. Together, these data provide novel mechanisms by which GLP-1R agonists in the mesolimbic reward system control for palatable food intake.

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Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1614340113 ◽

2016 ◽

Vol 113 (45) ◽

pp. 12826-12831 ◽

Cited By ~ 79

Author(s):

Norman E. Taylor ◽

Christa J. Van Dort ◽

Jonathan D. Kenny ◽

JunZhu Pei ◽

Jennifer A. Guidera ◽

...

Keyword(s):

General Anesthesia ◽

Ventral Tegmental Area ◽

Viral Vector ◽

Sch 23390 ◽

Reward Processing ◽

D1 Receptor ◽

Dopamine Neurons ◽

Behavioral Arousal ◽

Ventral Tegmental ◽

Processing Motivation

Dopamine (DA) promotes wakefulness, and DA transporter inhibitors such as dextroamphetamine and methylphenidate are effective for increasing arousal and inducing reanimation, or active emergence from general anesthesia. DA neurons in the ventral tegmental area (VTA) are involved in reward processing, motivation, emotion, reinforcement, and cognition, but their role in regulating wakefulness is less clear. The current study was performed to test the hypothesis that selective optogenetic activation of VTA DA neurons is sufficient to induce arousal from an unconscious, anesthetized state. Floxed-inverse (FLEX)-Channelrhodopsin2 (ChR2) expression was targeted to VTA DA neurons in DA transporter (DAT)-cre mice (ChR2+ group; n = 6). Optical VTA stimulation in ChR2+ mice during continuous, steady-state general anesthesia (CSSGA) with isoflurane produced behavioral and EEG evidence of arousal and restored the righting reflex in 6/6 mice. Pretreatment with the D1 receptor antagonist SCH-23390 before optical VTA stimulation inhibited the arousal responses and restoration of righting in 6/6 ChR2+ mice. In control DAT-cre mice, the VTA was targeted with a viral vector lacking the ChR2 gene (ChR2− group; n = 5). VTA optical stimulation in ChR2− mice did not restore righting or produce EEG changes during isoflurane CSSGA in 5/5 mice. These results provide compelling evidence that selective stimulation of VTA DA neurons is sufficient to induce the transition from an anesthetized, unconscious state to an awake state, suggesting critical involvement in behavioral arousal.

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Ethanol Inhibition of M-Current and Ethanol-Induced Direct Excitation of Ventral Tegmental Area Dopamine Neurons

Journal of Neurophysiology ◽

10.1152/jn.00270.2006 ◽

2007 ◽

Vol 97 (3) ◽

pp. 1977-1985 ◽

Cited By ~ 55

Author(s):

Susumu Koyama ◽

Mark S. Brodie ◽

Sarah B. Appel

Keyword(s):

Ion Channels ◽

Ventral Tegmental Area ◽

Firing Frequency ◽

Dopamine Neurons ◽

Dependent Manner ◽

Spontaneous Firing ◽

Concentration Dependent Manner ◽

Ethanol Inhibition ◽

M Current ◽

Ventral Tegmental

Ethanol-induced excitation of ventral tegmental area dopamine (DA VTA) neurons is thought to be critical for the reinforcing effects of ethanol. Although ligand-gated ion channels are known to be the targets of ethanol, ethanol modulation of voltage-dependent ion channels of central neurons has not been well studied. We have demonstrated that ethanol excites DA VTA neurons by the reduction of sustained K+ currents and recently reported that M-current ( IM) regulates action potential generation through fast and slow afterhyperpolarization phases. In the present study we thus examined whether ethanol inhibition of IM contributes to the excitation of DA VTA neurons using nystatin-perforated patch current- and voltage-clamp recordings. Ethanol (20–120 mM) reduced IM in a concentration-dependent manner and increased the spontaneous firing frequency of DA VTA neurons. Ethanol-induced increase in spontaneous firing frequency correlated positively with ethanol inhibition of IM with a slope value of 1.3. Specific IM inhibition by XE991 (0.3–10 μM) increased spontaneous firing frequency which correlated positively with IM inhibition with a slope value of 0.5. In the presence of 10 μM XE991, a concentration that produced maximal inhibition of IM, ethanol still increased the spontaneous firing frequency of DA VTA neurons in a concentration-dependent manner. Thus we conclude that, although ethanol causes inhibition of IM and this results in some increase in the firing frequency of DA VTA neurons, another effect of ethanol is primarily responsible for the ethanol-induced increase in firing rate in these neurons.

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