Striosomal ghrelin receptor activity controls reward-cost integration

Abstract

Growth hormone secretagogue receptors (GHSRs) modulate reward and cost processing separately, but their role in conflict-based decision-making is unclear. We observed dose-dependent effects of the GHSR agonist ibutamoren (IBU) on rat decision-making performance. Moderate, but not low or high doses, increased cost sensitivity selectively in conflict paradigms. We observed dense GHSR expression in dorsomedial striosomes, a region critical for conflict decision-making. Moderate GHSR activation increased neuronal activity in dorsomedial striosomes that project to lateral habenula (LHb) and enhanced inactivation of dopaminergic neurons in the substantia nigra pars compacta (daSNc). Chemogenetic manipulation of dorsomedial striosomes activity confirmed their causal influence on both GHSR-mediated increases in cost-sensitivity and circuit activity in LHb and daSNc. Our results identify a novel circuit mechanism linking endocrine activity with conflict decision-making.