Noradrenergic mechanisms in the nucleus accumbens shell as a gateway for the transition from impulsivity to compulsivity

Impulsivity represents an endophenotype of vulnerability to develop compulsive disorders such as drug addiction and obsessive compulsive disorder (OCD). However, the neural mechanisms that increase this vulnerability are unknown, thereby preventing the development of new effective therapeutic strategies.

We have demonstrated that the selective noradrenaline reuptake inhibitor atomoxetine prevents the transition from impulsivity to compulsivity in highly impulsive rats. The aim of this preliminary project is to provide proof of concept for a key contribution of the noradrenergic innervation of the nucleus accumbens shell (AbcS) from the nucleus tractus solitarius (NTS) to impulsivity and the associated increased vulnerability to develop OCD and other compulsive behaviours in rats.

We will demonstrate that noradrenergic mechanisms in the AcbS are involved in the well-established expression of compulsivity as measured using schedule-induced polydipsia (SIP), an established model of compulsivity. We will alsos identify noradrenergic correlates of impulsivity and compulsivity in the AcbS and demonstrate that specific optogenetic manipulation of the NTS-AcbS pathway influences impulsivity, compulsive adjunctive behaviour under SIP and compulsive relapse to seek cocaine in rats.