1. ¹Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH/DHHS, Baltimore, MD, USA
2. ²Division of Neuroscience and Behavior, Intramural Research Program, National Institute on Alcohol Abuse and Alcoholism, NIH/DHHS, Bethesda, MD, USA
3. ³Division of Nuclear Medicine, Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
4. ⁴Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA
5. ⁵Departments of Psychiatry and Biobehavioral Sciences, and Molecular and Medical Pharmacology, and the Brain Research Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
6. ⁶Department of Psychiatry and Behavioral Sciences, Center for Nicotine and Smoking Cessation Research, Duke University Medical Center, Durham, NC, USA

Correspondence: Dr AG Mukhin, Department of Psychiatry and Behavioral Sciences, Center for Nicotine and Smoking Cessation Research, Duke University Medical Center, 2424 Erwin Road, Suite 201, Durham, NC 27705, USA, Tel: +919 668 5092, E-mail: a.mukhin@duke.edu

Received 9 May 2006; Revised 22 February 2007; Accepted 23 February 2007; Published online 11 April 2007.

Abstract

To advance understanding of the neurochemical changes in Parkinson's disease (PD), we compared D2-like dopamine receptor occupancy by dopamine in the control and lesioned putamen of four pig-tailed macaques treated unilaterally with MPTP. PET and in vitro binding techniques were used to measure binding potential (BP^*) and density of D2-like dopamine receptors (B_max), respectively. As would be expected in PD, relatively higher values of BP^* and B_max and less amphetamine-induced decrease in [¹¹C]raclopride binding were observed in the lesioned compared with the contralateral putamen in each animal. The percent differences between lesioned and contralateral sides were similar whether the measurements were of [¹¹C]raclopride BP^* or B_max values, measured in vivo and in vitro, respectively. As [¹¹C]raclopride BP^* is a measure of the density of D2-like dopamine receptors available for radioligand binding (i.e., not occupied by dopamine), these findings suggest that the fractional occupancy of receptors by endogenous dopamine in the lesioned putamen is nearly equal to that in the contralateral putamen. Therefore, the absolute number of receptors occupied by dopamine, which is a product of receptor density and fractional occupancy by dopamine, is greater in the lesioned than in the contralateral putamen. One possible explanation for the lack of differences in fractional occupancy of D2 receptors by dopamine (despite a loss in available dopamine) is a lesion-induced increase in a portion of low-affinity D2 receptors to a state of high affinity for dopamine.