Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area

AbstractThe mesolimbic dopamine system comprises distinct compartments supporting different functions in learning and motivation. Less well understood is how complex addiction-related behaviors emerge from activity patterns across these compartments. Here we show how different forms of relapse to alcohol-seeking are assembled from activity across the ventral tegmental area and the nucleus accumbens. Using gCaMP and dLight fibre photometry, we show that self-administration and two forms of relapse (renewal/context-induced reinstatement and reacquisition) are associated with recruitment across the mesolimbic dopamine system. Using a variety of interventions, we show that this activity is causal to both forms of relapse. Finally, we use dissimilarity matrices to identify mesolimbic dopamine signatures of self-administration, extinction, and relapse. We show that signatures of relapse can be identified from heterogeneous activity profiles across the mesolimbic dopamine system and that these signatures differ for different forms of relapse.

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Tribute to: Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area [William Corrigall, Kathleen Coen and Laurel Adamson, Brain Res. 653 (1994) 278–284]

Brain Research ◽

10.1016/j.brainres.2015.12.064 ◽

2016 ◽

Vol 1645 ◽

pp. 61-64 ◽

Cited By ~ 3

Author(s):

Francesco Leri ◽

Franco J. Vaccarino

Keyword(s):

Ventral Tegmental Area ◽

Mesolimbic Dopamine ◽

Dopamine System ◽

Mesolimbic Dopamine System ◽

Ventral Tegmental

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Acute fasting increases somatodendritic dopamine release in the ventral tegmental area

Journal of Neurophysiology ◽

10.1152/jn.01008.2014 ◽

2015 ◽

Vol 114 (2) ◽

pp. 1072-1082 ◽

Cited By ~ 10

Author(s):

Aaron G. Roseberry

Keyword(s):

Ventral Tegmental Area ◽

Food Restriction ◽

Dopamine Release ◽

Dopamine Neurons ◽

Dopamine System ◽

Mesolimbic Dopamine System ◽

Axon Terminals ◽

Highly Active ◽

Target Sites ◽

Ventral Tegmental

Fasting and food restriction alter the activity of the mesolimbic dopamine system to affect multiple reward-related behaviors. Food restriction decreases baseline dopamine levels in efferent target sites and enhances dopamine release in response to rewards such as food and drugs. In addition to releasing dopamine from axon terminals, dopamine neurons in the ventral tegmental area (VTA) also release dopamine from their soma and dendrites, and this somatodendritic dopamine release acts as an autoinhibitory signal to inhibit neighboring VTA dopamine neurons. It is unknown whether acute fasting also affects dopamine release, including the local inhibitory somatodendritic dopamine release in the VTA. In these studies, I have tested whether fasting affects the inhibitory somatodendritic dopamine release within the VTA by examining whether an acute 24-h fast affects the inhibitory postsynaptic current mediated by evoked somatodendritic dopamine release (D2R IPSC). Fasting increased the contribution of the first action potential to the overall D2R IPSC and increased the ratio of repeated D2R IPSCs evoked at short intervals. Fasting also reduced the effect of forskolin on the D2R IPSC and led to a significantly bigger decrease in the D2R IPSC in low extracellular calcium. Finally, fasting resulted in an increase in the D2R IPSCs when a more physiologically relevant train of D2R IPSCs was used. Taken together, these results indicate that fasting caused a change in the properties of somatodendritic dopamine release, possibly by increasing dopamine release, and that this increased release can be sustained under conditions where dopamine neurons are highly active.

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