Estradiol Increases Choice of Cocaine over Food in Male Rats

Abstract

Women present more severe cocaine addiction profiles than men on some measures. Similarly, female rodents display greater cocaine intake under a variety of cocaine self‐administration schedules, including a choice self‐administration procedure in which subjects can choose between cocaine and food. Estradiol has been shown to largely mediate many of these sex effects, including cocaine choice. However, the effects of estradiol on male cocaine behavior are less studied. Male brains express estrogen receptors, and estradiol has been shown to modulate behaviors that share underlying neurobiology with cocaine reinforcement. Therefore, we sought to characterize the effects of estradiol in males, on choice behavior and on motivation for both cocaine and food in single‐reinforcer progressive ratio (PR) tests.MethodsMale castrated rats were treated daily with estradiol benzoate (EB) (5ug/0.1, S.C., n=23) or vehicle (peanut oil, n=23) throughout choice testing (3 grain food pellets, 1 mg/kg/infusion I.V. cocaine) and single‐reinforcer food and cocaine PR testing. Additionally, a subset of rats were tested in a modified choice procedure, in which the “cost” of the reinforcers were manipulated by escalating the fixed‐ratio (FR) requirement of the preferred reinforcer while maintaining the FR requirement of the non‐preferred reinforcer constant.ResultsEB increased cocaine intake in the choice test. EB subjects also demonstrated greater cocaine PR breakpoints, but had similar food PR breakpoints to controls. However, after a switch from home‐cage food restriction to ad libitum feeding, EB subjects increased food PR breakpoints while food PR breakpoints dropped in the control group. In the cost escalation test, cocaine preferring rats defended their cocaine intake to a greater degree than food preferring rats. There was no effect of EB on this measure. This suggests that, although estradiol increases the proportion of cocaine preferring rats in the choice procedure, EB does not further affect this measure.ConclusionThese results indicate that the effects of estradiol on choice behavior are not sex‐specific, estradiol increases the allocation of behavior towards cocaine in both sexes. Considering this concordant effect on behavior, the underlying neurobiology of choice behavior may be similarly affected by estradiol in both sexes.Support or Funding InformationNIDA (5R01DA027525‐05)