Treatment
In the United States alone there are 18 million alcoholics, 28 million children of alcoholics, 6 million cocaine addicts, 14.9 million people who abuse other substances, 25 million people addicted to nicotine, 54 million people who are at least 20 percent overweight, 3.5 million school-age children with attention-deficit disorder or Tourette syndrome, and about 448,000 compulsive gamblers. We believe that recognizing the role of dopamine and the D2 receptor in the manifestation of these addictions and disorders is the first step toward rational treatment for a devastating problem in our society.
There is reason to believe that a pharmacological approach could help people with reward deficiency syndrome. It is tempting to speculate that the pharmacological sensitivity of alcoholics to dopaminergic agonists (bromocriptine, bupropion and n-propylnor-apomorphine) may be partly determined by the individual's D2 genotoype. We predict that A1 carriers should be pharmacologically more responsive to D2 agonists, especially in the treatment of alcoholics or stimulant-dependent people. At least one study has already shown that the direct microinjection of the D2 agonist n-propylnor-apomorphine into the rat nucleus accumbens significantly suppresses the animal's symptoms after the withdrawal of opiates (Harris and Aston-Jones, 1994).
Genetics and Treatment
A recent double-blind study demonstrates the utility of this approach in human subjects (Lawford et al. 1995). The D2 agonist bromocryptine or a placebo was administered to alcoholics who were carriers of the A1 allele (A1/A1 and A1/A2 genotypes) or who only carried the A2 allele (A2/A2). The greatest improvement in the reduction of craving and anxiety was found among the A1 carriers who were treated with bromocryptine. The attrition rate was highest among the A1 carriers who were treated with the placebo.
These findings provide an important rationale for DNA testing to detect genetic variants for the D2 receptor or other dopamine-related genetic variants in the tertiary treatment of alcoholism. Unlike certain other complex disorders, such as Alzheimer's disease, the early identification and treatment of alcohol and drug abuse can occasionally alter the devastating course of these addictions. Consider the successes of self-help programs such as Alcoholics Anonymous and Narcotics Anonymous, psychopharmacological adjunctive therapy, neuroregulation or brain-wave training and electrophysiological stimulation. Identifying individuals with the A1 allele offers the possibility of helping individuals before alcoholism or substance abuse affect their lives. We foresee the possibility for better treatment, new forms of prevention and the removal of the social stigma attached not only to alcoholism but also to related "reward-seeking" behaviors comprising the reward deficiency syndrome.
