A disengaging property of medial accumbens shell dopamine

Electrical stimulation of the medial forebrain bundle vigorously reinforces self-stimulation behaviour, yet rodents perform operant responses to terminate this stimulation. The accumbens shell emerged as a substrate subserving the reinforcing properties of electrical medial forebrain bundle stimulation, whereas disengaging properties were attributed to incidentally recruited substrates near the electrode. Here, we examine whether there are dissociable reinforcing and disengaging properties of medial accumbens shell dopamine and probe the substrates underlying these properties. Using a temporally delimited self-stimulation procedure, transgenic DAT-Cre mice expressing channelrhodopsin-II in ventral tegmental area dopamine neurons were trained to hold-down a lever to engage, and then release the lever to disengage, optogenetic stimulation of dopaminergic inputs to the medial accumbens shell through an implanted optic fiber. The cumulative and mean duration of hold-downs show divergent frequency responses identifying dissociable reinforcing and disengaging properties of medial accumbens shell dopamine. At higher stimulation frequencies the cumulative duration of hold-downs grows, whereas the mean duration of hold-downs wanes. Dopamine agonists reduced the cumulative duration of self-stimulation hold-downs, but only a D1 agonist produced this reduction through decreases in the mean duration of hold-downs, which were lengthened with a D2 antagonist. Thus, reinforcing and disengaging properties of electrical medial forebrain stimulation may arise from the downstream activation of dopamine receptors, uncovering a disengaging property of medial accumbens shell dopamine. Significance Statement Dopamine is thought to promote behaviour by acting as a reinforcer or error signal. Here, we show that mice vigorously self-stimulate dopamine inputs to the medial accumbens shell but control the duration of duration of these stimulations and prefer them to be brief. This disengaging property of medial accumbens shell dopamine depends on downstream neurotransmission at dopamine type 1 and 2 receptors. Thus, a single dopaminergic substrate, inputs to the medial accumbens shell, reinforces and disengages self-stimulation behaviour, highlighting the complexity and regional specificity of striatal dopamine function. ### Competing Interest Statement The authors have declared no competing interest.