Use of positron emission tomography to measure the effects of nalmefene on D1 and D2 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 neuroreceptors. The present study evaluated the feasibility of performing high-resolution PET experiments in a rodent model to measure receptor kinetics. The effects of acute and chronic administration of the opioid antagonist, nalmefene, on the binding activity of [11C]SCH23390 and [11C]N-methylspiperone at D1 and D2 dopamine receptors, respectively, was investigated in the rat. The interaction between central opioid and dopaminergic 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 single 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 [11C]SCH23390 in the striatum was significantly increased. No changes in [11C]N-methylspiperone binding were found. Following chronic nalmefene administration, no significant change in either [11C]SCH23390 binding potential or [11C]N-methylspiperone binding was detected. These results suggest that nalmefene administration produces transient changes in the binding potential of D1-receptors in the striatum that are normalized after 1 week of steady-state administration.
Unterwald
E M
EM
Laboratory of the Biology of Addictive Diseases, Rockefeller University, New York, NY 10021, USA. unterwe@rockvax.rockefeller.edu
Tsukada
H
H
Kakiuchi
T
T
Kosugi
T
T
Nishiyama
S
S
Kreek
M J
MJ
D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D018491:Dopamine Agonists / Q000378:metabolism; D018492:Dopamine Antagonists / Q000378:metabolism; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D013134:Spiperone / Q000031:analogs & derivatives / Q000378:metabolism; D014055:Tomography, Emission-Computed
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D009292:Narcotic Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013134:Spiperone; D009271:Naltrexone; C039167:3-N-methylspiperone; C038981:nalmefene