Dissociating the reinforcing and sensory properties of medial accumbens shell dopamine

Abstract

AbstractElectrical stimulation of the medial forebrain bundle vigorously reinforces self-stimulation behaviour, yet rodents perform operant responses to terminate this stimulation. Whether distinct neural substrates underpin the reinforcing and sensory properties of electrical brain stimulation is a question that has hampered the development of efficacious treatment for psychopathology. The accumbens shell emerged as a substrate subserving the reinforcing and therapeutic properties of electrical medial forebrain bundle stimulation. Here, we examine whether there are dissociable reinforcing and sensory properties of medial accumbens shell dopamine and probe the substrates underlying these properties. Using a novel 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 sensory properties of dopamine’s actions in the medial accumbens shell. 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. Intense dopamine activity within the medial accumbens shell may achieve negative valence, disengaging behaviour through augmented neurotransmission at D1 receptors which proposes an adjuvant pharmacotherapy to enhance the treatment of binge eating and alcohol use disorder with electrical accumbens stimulation.