Predicting the effects of psychostimulants with D2 receptors

In 1999 Volkow et al injected carbon-11 radioisotoped raclopride into 23 males, an antagonist on dopamine family 2 (D2) receptors. After the radiotracer had seeped through the blood brain barrier, the researchers scanned them using PET to find time activity curves and thus quantify the amount of D2 receptors. On a later date they gave the same subjects a 0.5 mg/kg dose of methylphenidate (Ritalin), and quantified their responses to the drug. Subjects with lower levels of D2 receptors had significantly higher self-ratings of happiness, increases in mood, and lower self-ratings of annoyance and distrust.

Cocaine abusers have also found to have lower levels of D2 receptors than the rest of the population. It has been suggested that either users compensate for decreased activation of reward circuits with the drugs, or that low D2 users could on average enjoy the experience on the first time more, which is highly correlated with future use. Regardless of the specific mechanism, this is another data point suggesting that there is an optimal range of D2 receptor stimulation, where too little may be insufficient but too much may be aversive.

Reference

Volkow ND et al. 1999 Prediction of reinforcing responses to psychostimulants in humans by brain dopamine D2 receptor levels. Am J Psychiatry 156:1440-1443. Abstract.