Muscarinic receptor blockade in the ventral tegmental area attenuates cocaine enhancement of laterodorsal tegmentum stimulation-evoked accumbens dopamine efflux in the mouse

Synapse ◽  
2010 ◽  
Vol 64 (3) ◽  
pp. 216-223 ◽  
Author(s):  
Deranda B. Lester ◽  
Anthony D. Miller ◽  
Charles D. Blaha
Keyword(s):  
Ventral Tegmental Area ◽  
Muscarinic Receptor ◽  
Receptor Blockade ◽  
Ventral Tegmental ◽  
Laterodorsal Tegmentum ◽  
Dopamine Efflux

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 Ventral Tegmental Area Neurotensin Signaling Links the Lateral Hypothalamus to Locomotor Activity and Striatal Dopamine Efflux in Male Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (5) ◽  
pp. 1692-1700 ◽  
Author(s):  
Christa M. Patterson ◽  
Jenny-Marie T. Wong ◽  
Gina M. Leinninger ◽  
Margaret B. Allison ◽  
Omar S. Mabrouk ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Ventral Tegmental Area ◽  
Extracellular Fluid ◽  
Hypothalamic Area ◽  
Mass Spectrometry Technique ◽  
Spectrometry Technique ◽  
Ventral Tegmental ◽  
Dopamine Efflux ◽  
Physiologic State ◽  
Da Release

Projections from the lateral hypothalamic area (LHA) innervate components of the mesolimbic dopamine (MLDA) system, including the ventral tegmental area (VTA) and nucleus accumbens (NAc), to modulate motivation appropriately for physiologic state. Neurotensin (NT)-containing LHA neurons respond to multiple homeostatic challenges and project to the VTA, suggesting that these neurons could link such signals to MLDA function. Indeed, we found that pharmacogenetic activation of LHA NT neurons promoted prolonged DA-dependent locomotor activity and NAc DA efflux, suggesting the importance of VTA neurotransmitter release by LHA NT neurons for the control of MLDA function. Using a microdialysis-mass spectrometry technique that we developed to detect endogenous NT in extracellular fluid in the mouse brain, we found that activation of LHA NT cells acutely increased the extracellular concentration of NT (a known activator of VTA DA cells) in the VTA. In contrast to the prolonged elevation of extracellular NAc DA, however, VTA NT concentrations rapidly returned to baseline. Intra-VTA infusion of NT receptor antagonist abrogated the ability of LHA NT cells to increase extracellular DA in the NAc, demonstrating that VTA NT promotes NAc DA release. Thus, transient LHA-derived NT release in the VTA couples LHA signaling to prolonged changes in DA efflux and MLDA function.

scholarly journals Impairments in laterodorsal tegmentum to VTA projections underlie glucocorticoid-triggered reward deficits

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Bárbara Coimbra ◽  
Carina Soares-Cunha ◽  
Sónia Borges ◽  
Nivaldo AP Vasconcelos ◽  
Nuno Sousa ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Neuronal Activity ◽  
In Utero ◽  
In Utero Exposure ◽  
Optogenetic Stimulation ◽  
Ventral Tegmental ◽  
Laterodorsal Tegmentum ◽  
The Impact ◽  
Cholinergic Markers

Ventral tegmental area (VTA) activity is critical for reward/reinforcement and is tightly modulated by the laterodorsal tegmentum (LDT). In utero exposure to glucocorticoids (iuGC) triggers prominent motivation deficits but nothing is known about the impact of this exposure in the LDT-VTA circuit. We show that iuGC-rats have long-lasting changes in cholinergic markers in the LDT, together with a decrease in LDT basal neuronal activity. Interestingly, upon LDT stimulation, iuGC animals present a decrease in the magnitude of excitation and an increase in VTA inhibition, as a result of a shift in the type of cells that respond to the stimulus. In agreement with LDT-VTA dysfunction, we show that iuGC animals present motivational deficits that are rescued by selective optogenetic activation of this pathway. Importantly, we also show that LDT-VTA optogenetic stimulation is reinforcing, and that iuGC animals are more susceptible to the reinforcing properties of LDT-VTA stimulation.

Alpha1-adrenergic receptor blockade in the ventral tegmental area modulates conditional stimulus-induced cocaine seeking

2019 ◽  
Vol 158 ◽  
pp. 107680
Author(s):  
Wojciech B. Solecki ◽  
Michał Kielbinski ◽  
Karolina Karwowska ◽  
Katarzyna Zajda ◽  
Michał Wilczkowski ◽  
...  
Keyword(s):  
Ventral Tegmental Area ◽  
Conditional Stimulus ◽  
Adrenergic Receptor ◽  
Receptor Blockade ◽  
Cocaine Seeking ◽  
Ventral Tegmental ◽  
Adrenergic Receptor Blockade
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