Corticosteroid Receptor Modulation in the Dorsal Striatum Prevents Morphine-Induced Place Preference and Reduction in Dopamine Transporter (DAT) Immunoreactivity in Rats.

Stress hormones and corticosteroid signalling influence dopaminergic transmission and reward-related behaviours. The present study investigated whether pharmacological manipulation of corticosteroid signalling within the dorsal striatum influences morphine-induced conditioned place preference (CPP) and dopamine transporter (DAT) regulation. Male Wistar rats were implanted with bilateral intra-dorsal striatal cannulae and subjected to the CPP paradigm. Before conditioning sessions, animals received bilateral intra-dorsal striatal infusions of corticosterone, the glucocorticoid receptor (GR) antagonist RU-38486 or the mineralocorticoid receptor (MR) antagonist spironolactone. Behavioural preference, locomotor activity and DAT immunoreactivity were subsequently assessed. Morphine reliably induced CPP and reduced DAT immunoreactivity in the dorsal striatum. Corticosterone, RU-38486 and spironolactone each significantly attenuated morphine-induced CPP and prevented the reduction in DAT immunoreactivity without altering locomotor activity. The convergence of these pharmacologically distinct manipulations on similar behavioural and DAT outcomes suggests that perturbation of corticosteroid-sensitive signalling within the dorsal striatum modulates opioid reward and associated dopaminergic plasticity. Importantly, the present findings do not establish whether corticosterone's effect is mediated by classical GR signalling, rapid corticosteroid actions or GR-independent mechanisms. Given the role of the dorsal striatum in addiction-related learning and the transition towards habitual and compulsive drug seeking, these findings identify corticosteroid-dopamine interactions within this region as an important mechanism for further investigation in opioid use disorders.