Opioid abuse and brain gene expression

Opiate addiction is a central nervous system disorder of unknown mechanism. Neuronal basis of positive reinforcement, which is essential to the action of opioids, relies on activation of dopaminergic neurons resulting in an increased dopamine release in the mesolimbic brain structures. Certain aspects of opioid dependence and withdrawal syndrome are also related to the activity of noradrenergic and serotonergic systems, as well as to both excitatory and inhibitory amino acid and peptidergic systems. The latter pathways have been recently proven to be involved both in the development of dependence and in counteracting the states related to relapse. An important role in neurochemical mechanisms of opioid reward, dependence and vulnerability to addiction has been ascribed to endogenous opioid peptides, particularly those acting via the mu- and kappa-opioid receptors. Opiate abuse leads to adaptive reactions in the nervous system which occur at the cellular and molecular levels. Recent research indicates that intracellular mechanisms of signal transmission-from the receptor, through G proteins, cyclic AMP, MAP kinases to transcription factors-also play an important role in opioid tolerance and dependence. The latter link in this chain of reactions may modify synthesis of target genes and in this manner, it may be responsible for opiate-induced long-lasting neural plasticity. (C) 2004 Elsevier B.V. All rights reserved.