Acute Fasting Increases Somatodendritic Dopamine Release in the Ventral

25 Fasting and food restriction alter the activity of the mesolimbic dopamine system 26 to affect multiple reward-related behaviors. Food restriction decreases baseline 27 dopamine levels in efferent target sites and enhances dopamine release in response to 28 rewards such as food and drugs. In addition to releasing dopamine from axon 29 terminals, dopamine neurons in the ventral tegmental area (VTA) also release 30 dopamine from their soma and dendrites, and this somatodendritic dopamine release 31 acts as an auto-inhibitory signal to inhibit neighboring VTA dopamine neurons. It is 32 unknown whether acute fasting also affects dopamine release, including the local 33 inhibitory somatodendritic dopamine release in the VTA. In these studies, I have tested 34 whether fasting affects the inhibitory somatodendritic dopamine release within the VTA, 35 by examining whether an acute 24-hour fast affects the inhibitory post-synaptic current 36 mediated by evoked somatodendritic dopamine release (D2R IPSC). Fasting increased 37 the contribution of the first action potential to the overall D2R IPSC, and increased the 38 ratio of repeated D2R IPSCs evoked at short intervals. Fasting also reduced the effect 39 of forskolin on the D2R IPSC, and led to a significantly bigger decrease in the D2R 40 IPSC in low extracellular calcium. Finally, fasting resulted in an increase in the D2R 41 IPSCs when a more physiologically relevant train of D2R IPSCs was used. Taken 42 together, these results indicate that fasting caused a change in the properties of 43 somatodendritic dopamine release, possibly by increasing dopamine release, and that 44 this increased release can be sustained under conditions where dopamine neurons are 45 highly active. 46