Testosterone differentially alters cocaine-induced ambulatory and rearing behavioral responses in adult and adolescent rats

Abstract

Little is known about the physiological and behavioral effects of testosterone when co-administered with cocaine during adolescence. The present study aimed to determine whether exogenous testosterone administration differentially alters psychomotor responses to cocaine in adolescent and adult male rats. To this end, intact adolescent (30-days-old) and adult (60-day-old) male Fisher rats were pretreated with vehicle (sesame oil) or testosterone (5 or 10 mg/kg) 45 minutes prior to saline or cocaine (20 mg/kg) administration. Behavioral responses were monitored 1 hour after drug treatment, and serum testosterone levels were determined. Serum testosterone levels were affected by age: saline- and cocaine-treated adults in the vehicle groups had higher serum testosterone levels than adolescents rats, but after co-administration of testosterone the adolescent rats had higher serum testosterone levels than the adults. Pretreatment with testosterone affected baseline activity in adolescent rats: 5 mg/kg of testosterone increased both rearing and ambulatory behaviors in saline-treated adolescent rats. After normalizing data to % saline, an interaction between hormone administration and cocaine-induced behavioral responses was observed; 5 mg/kg of testosterone decreased both ambulatory and rearing behaviors among adolescents whereas 10 mg/kg of testosterone decreased only rearing behaviors. Testosterone pretreatment did not alter cocaine-induced behavioral responses in adult rats. These findings suggest that adolescents are more sensitive than adults to an interaction between testosterone and cocaine, and, indirectly, suggest that androgen abuse may lessen cocaine-induced behavioral responses in younger cocaine users.

Cross‐sensitization between testosterone and cocaine in adolescent and adult rats

“…Differently from our results, Minerly et al (2010) demonstrated that adolescent rats showed an increase in cocaine-induced locomotor activity after a single injection of testosterone propionate (5 or 10 mg/kg). In the same way, Martinez-Sanchis et al (2002) demonstrated, in adolescent mice, that acute testosterone administration resulted in increased locomotor response to cocaine.…”

“…The dose of cocaine used in these experiments is known to induce locomotor activity in the absence of focused stereotypy (Marin et al, 2008; Ushijima et al, 1995). The dose of testosterone was previously shown to change cocaine‐induced locomotor activity and is consistent with the abuse dosage used for humans (Martinez‐Sanchis et al, 2002; Minerly et al, 2010).…”

“…Taken together, these data suggest that testosterone-induced changes in cocaine behavioral effects during adolescence might depend on AAS type (testosterone propionate has a longer half-life as compared to testosterone) and the specie used. In addition, differences in the time interval between testosterone and cocaine injection could influence the result since Minerly et al (2010) analyzed the locomotor activity one hour after the acute injection of cocaine.…”

Effects of Progesterone and Testosterone on Cocaine Self-Administration and Cocaine Discrimination by Female Rhesus Monkeys

“…We were unable to locate any clinical studies of the interactions between cocaine and testosterone. As noted earlier, findings from preclinical studies of the effects of testosterone on cocaine-related increases in locomotor activity in rodents were inconsistent (Long et al, 1994;Martinez-Sanchis et al, 2002;Minerly et al, 2010). In this study, testosterone, like progesterone, produced a significant dose-dependent decrease in cocaine self-administration in female rhesus monkeys.…”

“…Testosterone was reported to enhance (Martinez-Sanchis et al, 2002;Minerly et al, 2010) and to prevent cocaineinduced locomotor activity (Long et al, 1994). Testosterone was reinforcing in rodents under some conditions (see for a review, Wood, 2004).…”