Frequency of cocaine administration affects behavioral and endocrine responses in male and female Fischer rats

Accumulating evidence has shown disparate behavioral responses to cocaine in male and female rats. To date, there is a lack of understanding of how cocaine administration frequency affects sexually dimorphic behavioral responses. In the present study we investigated the behavioral and endocrine responses to single (1 x 15 mg/kg) and "binge" (3 x 15 mg/kg) cocaine administration in male and female Fischer rats. Overall, females showed a more prolonged and robust behavioral response to both acute and "binge" pattern cocaine administration. Furthermore, sex-dependent behavioral topographies emerged during binge-pattern cocaine administration; female rearing activity increased across "binge" injections while ambulatory activity decreased. In contrast, male ambulatory and rearing behaviors remained constant across injections of "binge" cocaine. At the hormonal level, both single and "binge" pattern cocaine administration decreased testosterone levels in male rats. However, cocaine's modulation of testosterone levels was transient since testosterone levels were decreased by cocaine 30 min but not 3 hr following a single injection. In both male and female rats, "binge" cocaine increased plasma progesterone levels. However, acute cocaine administration increased progesterone levels transiently in only female rats. Our results show that pattern of administration affects both cocaine-stimulated behavioral and endocrine responses in male and female rats.