THE DOPAMINE D2 RECEPTOR GENE (DRD2) AND NEUROPSYCHIATRIC DISORDERS - THERAPEUTIC IMPLICATIONS

Epidemiological studies have demonstrated a significant positive correlation between attention deficit hyperactivity disorder (ADHD), a common childhood behavioural disorder, and the development of alcoholism or drug abuse in adulthood. Recent investigations have suggested that these disorders may be genetically determined. Dysfunction of the dopamine D-2 receptor gene (DRD2) has been identified as a possible genetic variation responsible for alterations in behaviour. Ongoing studies have indicated that variants of other dopamine receptor subtypes, such as D-3, and serotonin (5-hydroxytryptamine; 5-HT) metabolism may also be implicated in impulsive, compulsive and addictive behaviours. Such alterations in the genetic make-up result in functional deficiency of mesolimbic and frontal lobe dopamine metabolism. These findings provide a sound pharmacological basis for the treatment of ADHD with stimulants, such as methylphenidate and dexamphetamine (dextroamphetamine), and indicate that dopamine agonists may prove to be useful in the treatment of other impulsive, compulsive and addictive behaviours.