- 作者：Michael A. Nader ; Susan H. Nader ; Paul W. Czoty ; Natallia V. Riddick ; H. Donald Gage ; Robert W. Gould ; Br ; i L. Blaylock ; Jay R. Kaplan ; Pradeep K. Garg ; Huw M.L. Davies ; Daniel Morton ; Sudha Garg ; Beth A. Reboussin
- 关键词：Dopamine ; females ; PET imaging ; gender differences ; social rank ; vulnerability
- 刊名：Biological Psychiatry
- 出版年：2012
- 出版时间：1 September, 2012
- 年：2012
- 卷：72
- 期：5
- 页码：414-421
- 全文大小：919 K
Background
Brain imaging and behavioral studies suggest an inverse relationship between dopamine (DA) D2/D3 receptors and vulnerability to cocaine abuse, although most research has used males. For example, male monkeys that become dominant in a social group have significant elevations in D2/D3 receptor availability and are less vulnerable to cocaine reinforcement.Methods
DA D2/D3 receptor availability was assessed in female cynomolgus monkeys (n = 16) with positron emission tomography (PET) while they were individually housed, 3 months after stable social hierarchies had formed, and again when individually housed. In addition, PET was used to examine changes in dopamine transporter (DAT) availability after social hierarchy formation. After imaging studies were complete, monkeys received implantation with indwelling intravenous catheters and self-administered cocaine (.001-.1 mg/kg/injection) under a fixed-ratio 30 schedule of reinforcement. Acquisition of cocaine reinforcement occurred when response rates were significantly higher than when saline was self-administered.
Results
Neither DAT nor D2/D3 receptor availability in the caudate nucleus and putamen was predictive of social rank, but both significantly changed after formation of social hierarchies. DA D2/D3 receptor availability significantly increased in females that became dominant, whereas DAT availability decreased in subordinate females. Dominant female monkeys acquired cocaine reinforcement at significantly lower doses than subordinate monkeys.
Conclusions
The relationship between D2/D3 receptor availability and vulnerability to cocaine reinforcement seems, on the basis of these findings, opposite in females and males. These data indicate that the social environment profoundly affects the DA system but does so in ways that have different functional consequences for females than for males.