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 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 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

The Role of Ventral Tegmental Area Gamma-Aminobutyric Acid in Chronic Neuropathic Pain after Spinal Cord Injury in Rats

2018 ◽  
Vol 35 (15) ◽  
pp. 1755-1764 ◽  
Author(s):  
Moon Yi Ko ◽  
Eun Young Jang ◽  
June Yeon Lee ◽  
Soo Phil Kim ◽  
Sung Hun Whang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Ventral Tegmental Area ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Chronic Neuropathic Pain ◽  
Cord Injury ◽  
Ventral Tegmental

Modulatory role of the orexin system in stress‐induced analgesia: Involvement of the ventral tegmental area

2021 ◽  
Author(s):  
Kobra Askari ◽  
Shahrbanoo Oryan ◽  
Akram Eidi ◽  
Jalal Zaringhalam ◽  
Abbas Haghparast
Keyword(s):  
Ventral Tegmental Area ◽  
Ventral Tegmental

scholarly journals The laterodorsal tegmentum-ventral tegmental area circuit controls depression-like behaviors by activating ErbB4 in DA neurons

2021 ◽  
Author(s):  
Hongsheng Wang ◽  
Wanpeng Cui ◽  
Wenbing Chen ◽  
Fang Liu ◽  
Zhaoqi Dong ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Coping With Stress ◽  
Chemical Genetic ◽  
Chronic Social Defeat Stress ◽  
Ventral Tegmental ◽  
Laterodorsal Tegmentum ◽  
Specific Deletion

AbstractDopamine (DA) neurons in the ventral tegmental area (VTA) are critical to coping with stress. However, molecular mechanisms regulating their activity and stress-induced depression were not well understood. We found that the receptor tyrosine kinase ErbB4 in VTA was activated in stress-susceptible mice. Deleting ErbB4 in VTA or in DA neurons, or chemical genetic inhibition of ErbB4 kinase activity in VTA suppressed the development of chronic social defeat stress (CSDS)-induced depression-like behaviors. ErbB4 activation required the expression of NRG1 in the laterodorsal tegmentum (LDTg); LDTg-specific deletion of NRG1 inhibited depression-like behaviors. NRG1 and ErbB4 suppressed potassium currents of VTA DA neurons and increased their firing activity. Finally, we showed that acute inhibition of ErbB4 after stress attenuated DA neuron hyperactivity and expression of depression-like behaviors. Together, these observations demonstrate a critical role of NRG1-ErbB4 signaling in regulating depression-like behaviors and identify an unexpected mechanism by which the LDTg-VTA circuit regulates the activity of DA neurons.

scholarly journals GABA Site Agonist Gaboxadol Induces Addiction-Predicting Persistent Changes in Ventral Tegmental Area Dopamine Neurons But Is Not Rewarding in Mice or Baboons

2012 ◽  
Vol 32 (15) ◽  
pp. 5310-5320 ◽  
Author(s):  
E. Vashchinkina ◽  
A. Panhelainen ◽  
O. Y. Vekovischeva ◽  
T. Aitta-aho ◽  
B. Ebert ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Dopamine Neurons ◽  
Ventral Tegmental
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