Sex Differences in the Motivational Contrast between Sucrose and Cocaine in Rats

There are sex differences in the vulnerability to cocaine abuse and addiction. Understanding the differences is critical for developing the sex-tailored prevention and treatment strategies. Cocaine addiction is characterized by the pathological motivation for cocaine accompanied by the diminished motivation for natural rewards. Thus, the motivational impact of cocaine relative to natural rewards likely determines the attractiveness of cocaine and likely plays a role in the vulnerability to cocaine abuse and addiction. This study aimed to determine whether the relative magnitudes or contrast of the motivational impact between cocaine and sucrose is different between sexes. To this end, cocaine-naïve out bred Wistar rats were trained to self-administer sucrose pellets and the motivation for different amounts of sucrose was then determined as the breakpoints under the progressive-ratio schedule of reinforcement. Following the sucrose tests, the same rats were trained to self-administer cocaine and the motivation for different doses of cocaine was similarly measured. For the female rats, the motivation was also measured during the diestrus and proestrus/estrus, respectively, to determine the impact of the estrous cycle on the motivational effects of cocaine and sucrose. The differences between the breakpoints of cocaine and sucrose were significantly larger in the males. The enhanced motivational contrast may contribute to the increased vulnerability to recreational cocaine abuse and addiction in the males.