Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation

Abstract

Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1–D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated.

The Mesolimbic Dopamine System in Chronic Pain and Associated Affective Comorbidities

“…The NAc projects to various executive, emotional, and motor regions and is considered a master regulator of motivational drive (40,41). Although a decrease in NAc gray matter volume occurs in states of chronic pain (as with heroin addiction), the activity in this region collectively increases (30,(42)(43)(44).…”

Striatal dopamine regulates systemic glucose metabolism in humans and mice

“…After craniotomy, 0.5 l of AAV-DIO-Ef1a-hChR2(H134R)-EYFP (UNC Vector Core) was delivered bilaterally over 5 min by a 32-gauge Hamilton syringe. Transduction efficiency of this commercially available adeno-associated virus (AAV) construct has been demonstrated thoroughly (80). Immediately after infusion of the construct, fiber-optic cannulas (DFC_200/ 240-0.22_5mm_GS1.2_FLT; Doric Lenses) were implanted and secured to the skull using adhesive cement (C&B-METABOND S-380; Parkell).…”

Emerging roles of striatal dopamine D2 receptors in motivated behaviour: Implications for psychiatric disorders

“…Application of a brief, 1‐second optogenetic stimulation of either pathway during the cue light, which signalled the start of a PR trial, enhanced performace on the task. In contrast, optogenetic inhibition of indirect D2‐MSNs during the cue exposure was associated with decreased PR performance . Taken together, these experiments argue against an antagonistic relationship between the two pathways in the regulation of PR performance and suggest that synaptic inhibition of the ventral pallidum by D2‐MSNs promotes motivation …”

“…This is especially true in the NAc, where the degree of D1‐MSNs projecting to the pallidum is more pronounced relative to the dorsal striatum, prompting the suggestion of abolishing the use of “direct” and “indirect” pathway terminology in the NAc . In a similar vein, the prevailing view that assigns distinct and opposing roles to D1 and D2 receptors on accumbal‐related behaviours (eg stimulus‐reward processing) has been challenged by optogenetic studies suggesting both types of receptors are activated during reward‐based operant tasks …”

“…There is further evidence implicating both D1‐ and D2‐MSNs of medial shell and core of the NAc in enhancing progressive ratio performance . Using a Cre‐inducible channelrhodopsin 2 (ChR2) to specifically activate D1‐ or D2‐MSNs in the NAc of adult mice, the authors submitted mice to a progressive ratio schedule where a cue light indicated the active lever at the start of each PR trial.…”