Dependence reward pathways

Kreek, M. J. and Koob, G. F. Drug dependence stress and dysregulation of brain reward pathways. Drug Alcohol Depend. 51 23-47,1998. 

Wise RA (1987) The role of reward pathways in the development of drug dependence. Pharmacol... 

Accumulating electrophysiological and neuroanatomical analyses indicate that some of the CB, CNR receptor is targeted to the presynaptic terminals of neurons where it acts to inhibit release of classical neurotransmitters as reviewed by Elphick and Egertova, (2001). It is therefore tempting to speculate that the endocannabinoid system may be a major player in the reward pathway, particularly as it is one of the most abundant neurochemical systems in the CNS. Other studies report that THC, the major psychoactive constituent in marijuana, inhibits the synaptosomal uptake of dopamine, serotonin, norepinephrine, acetylcholine, and GABA. This, therefore, warrants pre-clinical evaluations to determine the role(s) of the endocannabinoid system in dmg and alcohol dependence and other neuropsychiatric conditions. 

Neurotransmission events involved in the sensation of reward are also important. Alcohol affects local concentrations of serotonin, opioids, and dopamine—neurotransmitters involved in brain reward circuits. Alcohol also has complex effects on the expression of receptors for these neurotransmitters and their signaling pathways. The discovery that naltrexone, a nonselective opioid receptor antagonist, helps patients who are recovering from alcoholism abstain from drinking supports the idea that the neurochemical reward system is shared by drugs associated with physical and psychological dependence. 

Opioid users are subject to the classic symptoms of physical dependence. These are increasing tolerance and the onset of physical withdrawal symptoms. Tolerance involves needing more of the drug as time passes to achieve the same desired results. Physical withdrawal can initiate within hours of the last use and consists of a cluster of flu-like symptoms. Withdrawal is mediated by neural pathways separate from those involving the reward system, causing withdrawal events to be perceived as life-threatening, and subsequent... 

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