USE OF POSITRON-EMISSION-TOMOGRAPHY TO MEASURE THE EFFECTS OF NALMEFENE ON D-1 AND D-2 DOPAMINE-RECEPTORS IN RAT-BRAIN

Positron emission tomography (PET) has been used in humans and in non- human primates to image and measure radioligand binding to neurorecept ors, The present study evaluated the feasibility of performing high-re solution PET experiments in a rodent model to measure receptor kinetic s, The effects of acute and chronic administration of the opioid antag onist, nalmefene, on the binding activity of [C-11]SCH23390 and [C-11] N-methylspiperone at D-1 and D-2 dopamine receptors, respectively, was investigated in the rat. The interaction between central opioid and d opaminergic systems has been the focus of much attention due to their interactive role in mediating reinforcement and locomotor activity. In the present study, adult male Sprague-Dawley rats received either a s ingle injection of 10 mg/kg of nalmefene or control vehicle solution 1 h prior to the PET scan or were chronically administered 10 mg/kg/day of nalmefene or vehicle for 7 days by an osmotic minipump. Following acute administration of nalmefene, the binding potential of [C-11]SCH2 3390 in the striatum was significantly increased. No changes in [C-11] N-methylspiperone binding were found. Following chronic nalmefene admi nistration no significant change in either [C-11]SCH23390 binding pote ntial or [11 C]N-methylspiperone binding was detected. These results s uggest that nalmefene administration produces transient changes in the binding potential of D-1-receptors in the striatum that are normalize d after 1 week of steady-state administration. (C) 1997 Elsevier Scien ce B.V.