2 - Neuroanatomical Bases of the Reinforcing Stimulus Effects of Cocaine

Abstract

In 1970s, Breese and Traylor described a method for selectively depleting brain catecholamines (dopamine and norepinephrine) using the neurotoxin 6-hydroxydopamine. Evidence for distinct behavioral functions of the nigrostriatal and mesolimbic dopaminergic pathways followed, as investigators targeted terminal regions of these pathways and isolated a role for dopamine rather than noradrenaline in behavioral effects of psychostimulants. In a study, five rats that had acquired stable cocaine self-administration behavior under a fixed ratio (FR) 1 schedule subsequently received neurotoxin 6-OHDA infusions that depleted accumbens dopamine by an average of 90% relative to control animals. Hoebel demonstrated that intra-accumbens amphetamine infusions reliably maintained responding in rats. The study highlighted several experiments providing evidence for reinforcing stimulus effects of intra-accumbens amphetamine infusions. Studies of 6-OHDA lesions aimed at determining the role of the mesocortical dopaminergic projection in the behavioral effects of cocaine have produced results similar to those described involving aspiration or excitotoxic lesions of medial prefrontal cortex. Investigations into the functional output of the nucleus accumbens established the ventral pallidal region as a critical mediator of the behavioral effects of psychomotor stimulants as well as opioids.