Radixin in the nucleus accumbens core modulates amphetamine-induced locomotor activity based on context association

Abstract

RationaleThe expression of addictive behaviors is linked to the structural plasticity of dendritic spines in the nucleus accumbens (NAcc). While radixin is known to contribute to morphological changes in dendritic spines, its role in the NAcc, specifically in the structural plasticity of dendritic spines and related drug-induced behavioral changes, is not well understood.ObjectiveIn the present study, we investigated the effects of radixin manipulation in the NAcc core on amphetamine (AMPH)-induced locomotor activity, both in association with and independent of a specific environment. Additionally, we examined the accompanying changes in dendritic spine density in this region.MethodsWe used a phosphomimetic pseudo-active mutant form (Rdx-T564D) and wild-type (Rdx-WT) radixin in conditioning and context-independent sensitization models induced by AMPH (1 mg/kg).ResultsWe observed that Rdx-T564D in the NAcc core selectively inhibited the expression of non-associative locomotor sensitization induced by AMPH. Conversely, overexpression of Rdx-WT in this region inhibited both conditioned locomotor activity and context-specific locomotor sensitization. Spine analysis revealed that the increase in mature thin spine density observed in the context-paired group was specifically suppressed by Rdx-WT, but not by GFP or Rdx-T564D.ConclusionsThis study revealed that associative and non-associative forms of AMPH-induced reward memory are differentially regulated by radixin manipulation in the NAcc core, suggesting a critical role of radixin in psychomotor stimulant addiction.