Positron emission tomographic measure of brain dopamine dependence to nicotine as a model of drugs of abuse.
BACKGROUND
Nicotine/tobacco are prototypic substances used throughout the world. Nicotine abstinence produces some depressive-like effects which are treated by the dopamine (DA) and norepinephrine reuptake inhibitor bupropion. A quantitative measure of the regional brain utilization of these catecholamines (CA) during nicotine dependence and withdrawal is important.


OBJECTIVE
The aim of this study was to prove that regional brain DA utilization by nicotine can be quantified by positron emission tomography (PET) using L-[beta-(11)C]DOPA.


METHODS
Eight young Macaca mulatta monkeys were given 0.9% NaCl or nicotine in doses of 32 or 100 microg/kg i.m. bid for 9 days to produce minimal dependence. On the tenth day, PET measurements were repeated before and after i.v. nicotine administration. PET studies were done in habituated, trained, and fully conscious animals.


RESULTS
Compared to a 0.9% NaCl control, acute i.v. nicotine as a bolus plus infusion for 30 min in similar doses to maintain a steady-state level for 30 min did not affect the utilization rate constant (k (3)) in dorsal or ventral striatum as measured by L-[beta-(11)C]DOPA. When monkeys were given nicotine bid repeatedly after overnight nicotine abstinence, CA utilization was reduced. A subsequent nicotine dose normalized utilization to slightly above control levels. Changes in ventral striatum were similar to those in dorsal striatum. The reduced rate of utilization demonstrated with L-[beta-(11)C]DOPA after overnight nicotine abstinence and its reversal by nicotine the next day provides an important PET measure of brain nicotine dependence and withdrawal. This method can be applied to other substances of abuse that release DA.
Domino
Edward F
EF
Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109-0632, USA. efdabcde@umich.edu
Tsukada
Hideo
H
Harada
Norihiro
N
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007980:Levodopa; D008253:Macaca mulatta; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D014029:Tobacco Use Disorder / Q000000981:diagnostic imaging / Q000378:metabolism*
D002250:Carbon Radioisotopes; D018722:Nicotinic Agonists; D007980:Levodopa; D009538:Nicotine; D004298:Dopamine