Frustrative nonreward and the basal ganglia: Chemogenetic inhibition and excitation of the nucleus accumbens and globus pallidus externus during reward downshift.

Frustrative nonreward induced by consummatory reward downshift (cRD) contributes to anxiety disorders and addiction, and is included in the Research Domain Criteria initiative as a relevant endophenotype. These experiments explored the role of the basal ganglia in cRD using inhibitory and excitatory DREADDs (designer receptors exclusively activated by designer drugs) infused in either the nucleus accumbens (NAc) or one of its downstream targets, the globus pallidus externus (GPe). NAc inhibition did not disrupt consummatory suppression during a 32-to-2% (Experiment 1) or 8-to-2% sucrose downshift (Experiment 2). However, NAc excitation enhanced consummatory suppression during a 32-to-2% sucrose downshift (Experiment 1). GPe inhibition caused a trend toward increased consummatory suppression after a 32-to-2% sucrose downshift, whereas GPe excitation eliminated consummatory suppression after an 8-to-2% sucrose downshift (Experiment 3). Chemogenetic manipulations of NAc and GPe had no detectable effects on open field activity. The effects of DREADD activation via clozapine N-oxide (CNO) administration were compared to controls that carried the DREADDs, but received vehicle injections. There was no evidence that CNO or vehicle injections in virus vector control (VVC) animals affected cRD or OF activity after either CNO or vehicle injections. NAc and GPe excitation led to opposite results in the cRD task, providing evidence that the basal ganglia circuit has a function in frustrative nonreward in the absence of motor effects.