scholarly journals Alpha-1 Adrenergic Receptors Modulate Glutamate and GABA Neurotransmission onto Ventral Tegmental Dopamine Neurons during Cocaine Sensitization

2020 ◽  
Vol 21 (3) ◽  
pp. 790 ◽  
Author(s):  
Maria Carolina Velasquez-Martinez ◽  
Bermary Santos-Vera ◽  
Maria E. Velez-Hernandez ◽  
Rafael Vazquez-Torres ◽  
Carlos A. Jimenez-Rivera
Keyword(s):  
Glutamate Release ◽  
Cell Voltage ◽  
Gaba Release ◽  
Dopamine Neurons ◽  
Gamma Aminobutyric Acid ◽  
Gabaergic Neurotransmission ◽  
Cocaine Administration ◽  
Ventral Tegmental ◽  
Gaba Neurotransmission

The ventral tegmental area (VTA) plays an important role in the reward and motivational processes that facilitate the development of drug addiction. Presynaptic α1-AR activation modulates glutamate and Gamma-aminobutyric acid (GABA) release. This work elucidates the role of VTA presynaptic α1-ARs and their modulation on glutamatergic and GABAergic neurotransmission during cocaine sensitization. Excitatory and inhibitory currents (EPSCs and IPSCs) measured by a whole cell voltage clamp show that α1-ARs activation increases EPSCs amplitude after 1 day of cocaine treatment but not after 5 days of cocaine injections. The absence of a pharmacological response to an α1-ARs agonist highlights the desensitization of the receptor after repeated cocaine administration. The desensitization of α1-ARs persists after a 7-day withdrawal period. In contrast, the modulation of α1-ARs on GABA neurotransmission, shown by decreases in IPSCs’ amplitude, is not affected by acute or chronic cocaine injections. Taken together, these data suggest that α1-ARs may enhance DA neuronal excitability after repeated cocaine administration through the reduction of GABA inhibition onto VTA dopamine (DA) neurons even in the absence of α1-ARs’ function on glutamate release and protein kinase C (PKC) activation. α1-AR modulatory changes in cocaine sensitization increase our knowledge of the role of the noradrenergic system in cocaine addiction and may provide possible avenues for therapeutics.

scholarly journals Role of the Medial Orbitofrontal Cortex and Ventral Tegmental Area in Effort-Related Responding

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Alexandra Münster ◽  
Angeline Votteler ◽  
Susanne Sommer ◽  
Wolfgang Hauber
Keyword(s):  
Ventral Tegmental Area ◽  
Orbitofrontal Cortex ◽  
Neural Circuit ◽  
Progressive Ratio ◽  
Dopamine Neurons ◽  
Gamma Aminobutyric Acid ◽  
Related Function ◽  
Pharmacological Inhibition ◽  
Ventral Tegmental

Abstract The posterior subdivision of the medial orbitofrontal cortex (mOFC-p) mediates the willingness to expend effort to reach a selected goal. However, the neural circuitry through which the mOFC-p modulates effort-related function is as yet unknown. The mOFC-p projects prominently to the posterior ventral tegmental area (pVTA). Therefore, we analyzed the role of the mOFC-p and interactions with the pVTA in effort-related responding using a combination of behavioral, pharmacological, and neural circuit analysis methods in rats. Pharmacological inhibition of the mOFC-p was found to increase lever pressing for food under a progressive ratio (PR) schedule of reinforcement. These findings provide further support for a modulation of effort-related function by the mOFC-p. Then, we investigated effects of disconnecting the mOFC-p and pVTA on PR responding using unilateral pharmacological inhibition of both areas. This asymmetric intervention was also found to increase PR responding suggesting that the mOFC-p controls effort-related function through interactions with the pVTA. Possibly, a reduced excitatory mOFC-p drive on pVTA gamma-aminobutyric acid (GABA)ergic relays disinhibits VTA dopamine neurons which are known to support PR responding. Collectively, our findings suggest that the mOFC-p and pVTA are key components of a neural circuit mediating the willingness to expend effort to reach a goal.

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

2017 ◽  
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.

scholarly journals The effects of early diabetes on inner retinal neurons

2020 ◽  
Vol 37 ◽  
Author(s):  
Erika D. Eggers ◽  
Teresia A. Carreon
Keyword(s):  
Ganglion Cells ◽  
Early Stage ◽  
Glutamate Release ◽  
Amacrine Cells ◽  
Gaba Release ◽  
Bipolar Cells ◽  
Gamma Aminobutyric Acid ◽  
Early Diabetes

Abstract Diabetic retinopathy is now well understood as a neurovascular disease. Significant deficits early in diabetes are found in the inner retina that consists of bipolar cells that receive inputs from rod and cone photoreceptors, ganglion cells that receive inputs from bipolar cells, and amacrine cells that modulate these connections. These functional deficits can be measured in vivo in diabetic humans and animal models using the electroretinogram (ERG) and behavioral visual testing. Early effects of diabetes on both the human and animal model ERGs are changes to the oscillatory potentials that suggest dysfunctional communication between amacrine cells and bipolar cells as well as ERG measures that suggest ganglion cell dysfunction. These are coupled with changes in contrast sensitivity that suggest inner retinal changes. Mechanistic in vitro neuronal studies have suggested that these inner retinal changes are due to decreased inhibition in the retina, potentially due to decreased gamma aminobutyric acid (GABA) release, increased glutamate release, and increased excitation of retinal ganglion cells. Inner retinal deficits in dopamine levels have also been observed that can be reversed to limit inner retinal damage. Inner retinal targets present a promising new avenue for therapies for early-stage diabetic eye disease.

scholarly journals Role of the bed nucleus of the stria terminalis in the control of ventral tegmental area dopamine neurons

2009 ◽  
Vol 33 (8) ◽  
pp. 1336-1346 ◽  
Author(s):  
Marion Jalabert ◽  
Gary Aston-Jones ◽  
Etienne Herzog ◽  
Olivier Manzoni ◽  
François Georges
Keyword(s):  
Ventral Tegmental Area ◽  
Dopamine Neurons ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Ventral Tegmental

scholarly journals Alpha‐1 adrenoreceptors modulate GABA release onto ventral tegmental area dopamine neurons

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Maria Carolina Velasquez ◽  
Rafael Vazquez ◽  
Priscila Sanabria ◽  
Carlos A. Jimenez‐Rivera
Keyword(s):  
Ventral Tegmental Area ◽  
Gaba Release ◽  
Dopamine Neurons ◽  
Ventral Tegmental

scholarly journals Alpha-1 adrenoreceptors modulate GABA release onto ventral tegmental area dopamine neurons

2015 ◽  
Vol 88 ◽  
pp. 110-121 ◽  
Author(s):  
Maria C. Velásquez-Martínez ◽  
Rafael Vázquez-Torres ◽  
Legier V. Rojas ◽  
Priscila Sanabria ◽  
Carlos A. Jiménez-Rivera
Keyword(s):  
Ventral Tegmental Area ◽  
Gaba Release ◽  
Dopamine Neurons ◽  
Ventral Tegmental

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

2020 ◽  
Vol 11 (6) ◽  
pp. 773-780
Author(s):  
Farzaneh Saebi Rad ◽  
◽  
Abbas Haghparast ◽  
Afsaneh Eliassi ◽  
◽  
...  
Keyword(s):  
Food Intake ◽  
Ventral Tegmental Area ◽  
Dopamine Receptors ◽  
Glutamate Release ◽  
D1 Receptor ◽  
Dopamine Neurons ◽  
Dependent Manner ◽  
Regulatory Pathways ◽  
Serotonergic Receptors ◽  
Ventral Tegmental

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.

scholarly journals Cortical and raphe GABAA, AMPA receptors and glial GLT-1 glutamate transporter contribute to the sustained antidepressant activity of ketamine

2020 ◽  
Author(s):  
Thu Ha Pham ◽  
Céline Defaix ◽  
Thi Mai Loan Nguyen ◽  
Indira Mendez-David ◽  
Laurent Tritschler ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Forced Swim Test ◽  
Glutamate Release ◽  
Glutamate Transporter ◽  
Antidepressant Activity ◽  
Gaba Release ◽  
Nmda Receptor Antagonist ◽  
Post Dose ◽  
Rapid Responses

ABSTRACTAt sub-anaesthetic doses, ketamine, a non competitive N-methyl-d-aspartate (NMDA) receptor antagonist, has demonstrated remarkable and rapid antidepressant (AD) efficacy in patients with treatment-resistant depression (TRD). However, its mechanism of action of ketamine is not fully understood. Since comorbid depression and anxiety disorders often occur, GABAergic/inhibitory and glutamatergic/excitatory drug treatments may be co-administered in these patients. Information regarding this combination is critical to establish efficacy or treatment restrictions to maximize translation from animal models to TRD patients, effectiveness and safety. To assess the specific role of excitatory/inhibitory neurotransmission in the medial prefrontal cortex-raphe nuclei (mPFC-DRN) circuit in the sustained antidepressant-like activity (AD) of ketamine (at t24h post dose), AMPA-R antagonist (intra-DRN) and GABAA-R agonist (intra-mPFC) were co-administered with ketamine (intra-mPFC). Twenty-four hours later, responses in the forced swim test (FST) and neurochemical consequences on extracellular mPFC glutamate, GABA and 5-HT levels were measured in BALB/cJ mice. Intra-DRN NBQX prevented the sustained AD-like activity of ketamine evidenced by decreases in FST swimming duration and blunted cortical 5-HText and Gluext. Intra-mPFC muscimol blocked ketamine AD-like activity and its effects on cortical 5-HText. Moreover, a selective glutamate transporter GLT-1 inhibitor, dihydrokainic acid (DHK) locally perfused into the mPFC produced an AD-like activity at t24h associated with robust increases in mPFC 5-HText, Gluext and GABAext. Thus, the sustained AD-like activity of ketamine is triggered by AMPA-R activation in the DRN and 5-HT - glutamate release in the mPFC, but limited by GABAA-R activation - GABA release in the mPFC. The local blockade of GLT-1 in the mPFC also mimics the rapid responses of ketamine, thus highlighting the role of neuronal-glial adaptation in these effects. These results also suggests the need to test for the concomitant prescription of ketamine and BZD to see whether its sustained antidepressant activity is maintained in TRD patients.

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