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 10mg/kg) 45 min prior to saline or cocaine (20mg/kg) administration. Behavioral responses were monitored 1h 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 adolescent 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: 5mg/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; 5mg/kg of testosterone decreased both ambulatory and rearing behaviors among adolescents whereas 10mg/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.

Figure 1. Serum testosterone levels after acute testosterone administration

Data represent mean ± SEM serum levels of testosterone for both adult (square symbols) and adolescent (circular symbols) male rats in cocaine-treated (solid line, solid symbols) or saline-treated (dotted line, empty symbols) groups. *Represents statistically significant differences between saline and cocaine treatments. #Represents statistically significant differences between adolescent and adult rats. N=8–12 per group.

Figure 2. Time course analysis of ambulatory (A) and rearing counts (B) in vehicle-treated adult and adolescent intact male rats after cocaine administration

Data represent mean ± SEM behavioral responses over a 1-hour period (5-minute intervals) in adult (square symbols) and adolescent (circular symbols) male rats in cocaine-treated (solid line, solid symbols) or saline-treated (dotted line, empty symbols) groups. *Represents statistically significant differences between saline and cocaine treatments. N= 8–12 per group.

Figure 3. Ambulatory (A, B) and rearing (C, D) behavioral responses in adult and adolescent intact male rats after acute testosterone and cocaine administration

Data in A and C represent the sum of mean± SEM behavioral responses across 1 hour after saline (white bars) or cocaine (solid bars) treatment. Data in C and D represent mean %-change ± SEM behavioral responses. Behavior was recorded for 1 hour after drug treatment. ^Represents statistically significant differences between testosterone doses. *Represents statistically significant differences of %-change between testosterone doses. #Represents statistically significant differences between saline plus testosterone treated groups. N= 8–12 per group.

Figure 4. Stereotypic activity, expressed as median stereotypic scores for adolescent and adult male rats after acute testosterone and cocaine administration

Activity was recorded for 30 seconds, 30 minutes after cocaine injection. Data represent stereotypic score as determined by three blinded observers for saline-treated (white bars) and cocaine-treated (black bars) animals. *Represents statistically significant differences between saline and cocaine treatments. N= 8–12 per group.