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 D-2 receptors in vivo in rat striatum, and may enhance the response to subsequent amphetamine challenge doses, was examined. The in vivo binding potentials of [C-11]raclopride, a D-2 receptor antagonist, were determined in male CD-1 rats under five conditions: (1) drug-naive with saline challenge, (2) drug naive 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 [C-11]raclopride binding was increased by 63% compared to saline-treated controls. The response to an amphetamine challenge, evidenced by a reduction of [C-11]raclopride binding, was doubled in amphetamine-dosed animals (40%) compared to drug-naive controls (20%). These results support increased baseline in vivo dopamine D-2 receptor antagonist radioligand binding after repeated amphetamine administration in rats. (C) 2011 Elsevier B.V. All rights reserved.