Brain reinforcement mechanisms of alcohol.: II.: Neurochemical basis:: Role of the opioid system.

Numerous evidence suggest the existence of a biological component in the brain reinforcement mechanisms elicited by alcohol. Neuroscience research has focused on the investigation of the neural substrates and the neurotransmitter systems involved in these mechanisms. Several studies show that brain dopaminergic, serotoninergic and opioid systems play a key role in these processes. Alcohol increases dopaminergic and serotoninergic transmission in brain regions linked to reward pathways. Dopaminergic and serotoninergic agonist administration reduces alcohol intake, whereas dopaminergic antagonist administration increases it. Some studies suggest that D-2, 5-HT1A and 5-HT3 receptors may participate in these responses. Alcohol and opioid peptides share many pharmacological characteristics and show similar effects on behavior in animals and man. The opioid system has been postulated to mediate alcohol positive reinforcement effects. Alcohol intake is altered by the administration of exogenous opioid peptides and the activity of the opioid system is in turn affected by alcohol. Ethanol modifies the synthesis and release of some opioid peptides as well as the activity of mu and delta opiate receptors. On the other hand, the administration of selective mu and delta opiate receptor antagonists reduces alcohol preference and intake in animals. Opiate antagonists like naltrexone reduce the reinforcing properties of alcohol in social drinkers and decrease the excessive intake of the substance. Consequently, it is possible that alcohol preference may be associated with an enhanced activation of the opioid system. The development of pharmacological agents able to modify the transmission of opioid peptides, as well as that of other neurotransmitters in the brain, has a potential therapeutic use in the treatment of alcoholism in humans.