Drug addiction resembles a chronic relapsing disorder. A complex interaction of environmental and genetic factors underlie the pathogenesis of the disease. Experimental paradigms in which animals learn to self-administer drugs abused by humans have recently given considerable insight into the biochemical, anatomofunctional, and behavioral mechanisms of addiction. In this respect, the mesolimbic dopamine system, and the nucleus accumbens (NAc) in particular, has been shown to play a key role in drug abuse processes. Indeed, drugs of abuse belonging to different pharmacological classes preferentially increase dopamine transmission in NAc with respect to the dorsal striatum. The functional anatomy of NAc has been revised recently with the identification of a ventromedial "shell," considered the most rostral component of the "extended amygdala," and a laterodorsal "core," viewed as portion of the striatopallidal complex. These two portions have been also assigned different functions, the shell playing a role in motivation and emotions and the core being involved in somato-motor processes. Thus, the question arises as to whether drugs of abuse affect the two portions of NAc differently. Recent studies from our group showed that intravenous administration of several drugs of abuse (psychomotor stimulants, opiates, nicotine, and cannabinoids) consistently increases extracellular dopamine levels (measured by intracerebral microdialysis) and local cerebral glucose utilization (measured by the [14C]2-deoxyglucose autoradiographic technique) in the rat NAc shell, with little or no effect in the 'core'. Interestingly, these changes were measured using doses of each drug that are known to maintain self-administration behavior in the rat. When present, changes in the core were obtained with higher doses of drugs that increased motor activity. These results indicate a common neural substrate for the rewarding effect of drugs of abuse, independently from the specific neurochemical action of each substance. Moreover, they show that increased dopamine transmission and energy metabolism in the NAc shell occur at doses that do not stimulate motor activity. Thus, increased dopamine transmission and energy metabolism in the 'shell' may subserve cognitive and emotional processes related to the interaction with drugs of abuse that underlie the neural basis of addiction. Recent human studies suggest that similar mechanisms occur in the disease.
|Issue number||4 SUPPL.|
|Publication status||Published - 2000|
ASJC Scopus subject areas
- Clinical Neurology