Alterations in Striatal Circuits Underlying Addiction-Like Behaviors

Abstract

Drug addiction is a severe psychiatric disorder characterized by the compulsive pursuit of drugs of abuse despite potential adverse consequences. Although several decades of studies have revealed that psychostimulant use can result in extensive alterations of neural circuits and physiology, no effective therapeutic strategies or medicines for drug addiction currently exist. Changes in neuronal connectivity and regulation occurring after repeated drug exposure contribute to addiction-like behaviors in animal models. Among the involved brain areas, including those of the reward system, the striatum is the major area of convergence for glutamate, GABA, and dopamine transmission, and this brain region potentially determines stereotyped behaviors. Although the physiological consequences of striatal neurons after drug exposure have been relatively well documented, it remains to be clarified how changes in striatal connectivity underlie and modulate the expression of addiction-like behaviors. Understanding how striatal circuits contribute to addiction-like behaviors may lead to the development of strategies that successfully attenuate drug-induced behavioral changes. In this review, we summarize the results of recent studies that have examined striatal circuitry and pathway-specific alterations leading to addiction-like behaviors to provide an updated framework for future investigations.

Keywords: addiction-like behaviors; circuit-specific modulation; drug addiction; striatal circuits.

Fig. 1

Diverse afferent and efferent connectivity in the striatum. Medial PFC, medial prefrontal cortex; PrL, prelimbic cortex; IL, infralimbic cortex; vHPC, ventral hippocampus; DMS, dorsomedial striatum; DLS, dorsolateral striatum; NAc, nucleus accumbens; BLA, basolateral amygdala; D1R, dopamine receptor type 1; D2R, dopamine receptor type 2; VTA, ventral tegmental area; SNpc, substantia nigra pars compacta; Glut/DA, glutamate and dopamine co-transmission (not discussed in this review).

Fig. 2

Distinct striatal circuits involved in the progression of addiction-like behaviors. Each pathway (represented by numbers) has been examined using optogenetic or chemogenetic modulation to determine its physiological contribution to the various addiction progression phases.