ABSTRACT
The reward substrates of the central nervous system (CNS) consist of: (1) a core dopaminergic/enkephalinergic neural system synaptically interconnecting the ventral tegmental area, nucleus accumbens, and ventral pallidum, and which appears to mediate reinforcement; (2) a glutamatergic neural network originating in the frontal cortex and deep temporal lobe, which feeds into the core dopaminergic/enkephalinergic system and which appears to mediate aspects of reward-related incentive motivation; and (3) additional neural inputs – which use many different neurotransmitters, including 5-hydroxytryptamine (serotonin), gammaaminobutyric acid (GABA), and dynorphin – into the core dopaminergic/enkephalinergic system, which appear to regulate additional aspects of reward. These complex and interrelated systems are strongly implicated in drug addiction, and in such addiction-related phenomena as withdrawal dysphoria and craving. These systems are also implicated in the pleasures produced by such natural rewards as food and sex. On the basis of more than 15 years of work, cannabinoids are now known to activate these CNS substrates and influence reward-related behaviors. From these actions, presumably, derive both the addictive potential of cannabinoids and possible clinical benefit in mood disorders such as depression.
