Increased in vivo [11C]raclopride binding to brain dopamine receptors in amphetamine-treated rats

The hypothesis that repeated daily doses of amphetamine increases the number of available dopamine D2 receptors in vivo in rat striatum, and may enhance the response to subsequent amphetamine challenge doses, was examined. The in vivo binding potentials of [11C]raclopride, a D2 receptor antagonist, were determined in male CD-1 rats under five conditions: (1) drug-naïve with saline challenge, (2) drug naïve with 5 mg/kg amphetamine challenge, (3) amphetamine-dosed (five daily repeated s.c. doses of 5 mg/kg amphetamine) and saline challenge, (4) amphetamine-dosed and amphetamine challenge, and (5) saline treated (five daily repeated s.c. doses) and saline challenged. Radiotracer studies in amphetamine-dosed animals were done after a 10-day drug free interval. In the amphetamine-dosed group the baseline [11C]raclopride binding was increased by 63% compared to saline-treated controls. The response to an amphetamine challenge, evidenced by a reduction of [11C]raclopride binding, was doubled in amphetamine-dosed animals (40%) compared to drug-naïve controls (20%). These results support increased baseline in vivo dopamine D2 receptor antagonist radioligand binding after repeated amphetamine administration in rats.