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

Numerous evidence suggest the existence of a biological component in the br ain reinforcement mechanisms elicited by alcohol. Neuroscience research has focused on the investigation of the neural substrates and the neurotransmi tter systems involved in these mechanisms. Several studies show that brain dopaminergic, serotoninergic and opioid systems play a key role in these pr ocesses. Alcohol increases dopaminergic and serotoninergic transmission in brain reg ions linked to reward pathways. Dopaminergic and serotoninergic agonist adm inistration reduces alcohol intake, whereas dopaminergic antagonist adminis tration increases it. Some studies suggest that D-2, 5-HT1A and 5-HT3 recep tors 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 th e activity of the opioid system is in turn affected by alcohol. Ethanol mod ifies the synthesis and release of some opioid peptides as well as the acti vity of mu and delta opiate receptors. On the other hand, the administratio n of selective mu and delta opiate receptor antagonists reduces alcohol pre ference and intake in animals. Opiate antagonists like naltrexone reduce th e reinforcing properties of alcohol in social drinkers and decrease the exc essive intake of the substance. Consequently, it is possible that alcohol p reference may be associated with an enhanced activation of the opioid syste m. The development of pharmacological agents able to modify the transmission o f opioid peptides, as well as that of other neurotransmitters in the brain, has a potential therapeutic use in the treatment of alcoholism in humans.