Dopamine Receptor - Dopamine Regulation

Dopamine Regulation

Dopamine receptors are typically stable, however sharp (and sometimes prolonged) increases or decreases in dopamine levels (via stimulants or antipsychotics mainly) can downregulate (reduce the numbers of) or upregulate (increase the numbers of) dopamine receptors. With stimulants, downregulation is typically associated with loss of interest in pleasureable activities, shortened attention span, and drug seeking behavior. With antipsychotics, associated upregulation can cause temporary dyskinesia, or tardive dyskinesia (fine muscles e.g. facial muscles, twitch involuntarily).

Haloperidol, and some other antipsychotics, have been shown to increase the binding capacity of the D₂ receptor when used over long periods of time (i.e. increasing the number of such receptors). Haloperidol increased the number of binding sites by 98% above baseline in the worst cases, and yielded significant dyskinesia side effects.

There are differing reports of abused stimulants, and up/down regulation. According to one study, cocaine, heroin, amphetamine, alcohol, and nicotine cause decreases in D₂ receptor quantity. A similar association has been linked to food addiction, with a low availability of dopamine receptors present in people with greater food intake. A recent news article summarized a U.S. DOE Brookhaven National Laborotory study showing that increasing dopamine receptors with genetic therapy temporarily decreased cocaine consumption by up to 75%. The treatment was effective for 6 days.

A contrasting study of cocaine shows that cocaine upregulates D₃ receptors in the nucleus accumbens, possibly contributing to drug seeking behavior.

Working memory training has been associated with dopamine D₁ receptor downregulation, which is believed to have an important role in working memory tasks.