Frustrative nonreward and the basal ganglia: Function of nucleus accumbens and globus pallidus externus during consummatory reward downshift

Guarino, Sara

Publication

Frustrative nonreward and the basal ganglia: Function of nucleus accumbens and globus pallidus externus during consummatory reward downshift

Guarino, Sara

Date

12/6/2021

Abstract

The role of the nucleus accumbens (NAc) and globus pallidus externus (GPe) in the adjustment to the consummatory reward downshift (cRD) and in open field (OF) activity was studied using designer receptors exclusively activated by designer drugs (DREADDs). Rats exposed to unexpected sucrose downshifts exhibit significant suppression of licking response to the downshifted sucrose solution relative to unshifted controls always given access to the same sucrose solution. This effect was replicated in Experiment 1. A 32-to-2% sucrose downshift induced significant suppression of licking relative to an unshifted 2% sucrose controls. Groups of rats received bilateral infusion of the inhibitory or excitatory designer receptors into the NAc (Experiments 2a-b) and GPe (Experiment 3). NAc excitation, using the DREADD activator clozapine N-oxide (CNO) to activate receptors, led to reduced licking in early 32-to-2% downshift sessions, whereas NAc inhibition, using CNO to activate receptors, did not have significant effects on 32-to-2% and 8-to-2% sucrose downshifts in the RD situation. NAc chemogenetic manipulations did not produce detectable effects in the OF task. GPe enhanced consummatory suppression in early 32-to-2% sucrose downshift sessions, without affecting late downshift session. By contrast, GPe excitation led to reduced consummatory suppression in early 8-to-2% sucrose downshift sessions, and enhanced suppression in late downshift sessions. These chemogenetic manipulations of GPe neurons also had no detectable effects on OF activity. First, NAc experiments are the first to show effects of chemogenetic manipulations of NAc in the RD task. Results of NAc chemogenetic inhibition corroborated findings from NAc lesion studies. NAc chemogenetic excitation experiment is the first to identify a function for NAc neurons in reward loss. These effects occurred in absence of any evidence of motor alterations after either inhibitory or excitatory DREADD activation in the OF task. Second, GPe experiments are the first to show an effect of chemogenetic manipulation of GPe neurons on behavior during sucrose downshift events. This research is the first to demonstrate an inhibitory role of the NAc in response to reward loss, and a role of the GPe in frustrative nonreward, a pattern of findings that encourages further investigation of basal ganglia functions in frustration.