Reward system and drug dependence

Abstract

A neural circuitry which could be the anatomical and neurochemical substrate for pleasure, reward and drug dependence was described four decades ago. Some lab animals are able of compulsive electrical self-stimulation or drug self-administration affecting the nucleus of this circuit, and thus showing a behavior interpreted as pleasure. If pemitted, they would permanently seek for this behavior, abandoning feeding or sex. The nucleus accumbens, the hippocampus, the prefrontal cortex, and the amygdala are the relevant areas of this system.The nucleus accumbens has been suggested as a critical neuronal part for drug reinforcement and drug dependence. Its afferents, involved in the regulation of drug reinforcement, arise from cortical structures of which the prefrontal cortex, the hippocampus, and the amygdaloid complex provide the densest input.The efferent projections from the nucleus accumbens involved in these behavioral events are the ventral pallidum, and the mesencefalic motors (nuclei from which the efferents go to the spinal cord).This efferent pathway helps control motor behaviour. Dopamine has been pointed out as the principal triggering neurotransmitter to initiate and also maintain reward and drug dependence in these pathways. However, support for the role of GABA, glutamate, aspartate and, very recently, nitric oxide in this pleasure and reward system is reviewed here.