SEX DIFFERENCES IN ADDICTION: PRECLINICAL STUDIES OF NEURAL MECHANISMS.

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Becker, J B1

1 Department of Psychology and Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI USA

Addiction is characterized by compulsive drug taking that supersedes other recreational, occupational or social pursuits. Sex differences in the motivation to take drugs of abuse and the escalation of drug taking behavior are seen for all classes of abused drugs in humans and rodents. Using the rat as an animal model, we find that in females there are rapid effects of estradiol on the ascending dopamine system that enhance the female’s motivation to engage in these behaviors. Female rats exhibit greater behavioral sensitization to cocaine, acquire cocaine self-administration more rapidly, and work harder to receive cocaine than males, and estradiol enhances these sex differences. We find that rats vulnerable to addiction can be identified, within the larger population, based on their preference for cocaine over palatable food rewards. These cocaine-preferring rats increase their drug intake at the expense of pellets, displayed greater motivation for cocaine, attenuated motivation for pellets and an attenuated cocaine-induced dopamine release in nucleus accumbens, compared with animals that preferred palatable food pellets. Finally, females are more likely to develop this cocaine preference than are males. These findings will be discussed within the larger context of sex differences in addiction.

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