Reduced sensitivity to reinforcement in adolescent compared to adult Sprague-Dawley rats of both sexes

Abstract

RATIONALE: Adolescence is a period of considerable development of brain and behavior and is the time during which most drug use is initiated. OBJECTIVE: Age-dependent differences in motivated behaviors may be one of the factors that contribute to heightened vulnerability to developing substance use disorders, so we sought to compare age differences in methamphetamine (METH) and saccharin seeking. METHODS: Beginning during adolescence or adulthood, male and female Sprague-Dawley rats were trained to self-administer 0.1% saccharin (via liquid dipper cup) or intravenous METH at one of three doses (0.02, 0.05, 0.08 mg/kg/inf) under increasing fixed ratio schedules of reinforcement. Subsequently, responding for METH (0.02, 0.05, 0.08 or 0.1 mg/kg/inf) under progressive ratio response requirements was assessed in rats that acquired METH self-administration at the highest dose (0.08 mg/kg/inf). RESULTS:We found that adult-onset rats acquired METH self-administration more readily and exhibited higher motivation compared to adolescent-onset rats, although there were no differences in METH intake during acquisition. Adult rats also acquired saccharin selfadministration more readily, but in contrast to METH, there were age and sex differences in saccharin intake driven by high levels of responding in adult females. CONCLUSIONS: These findings challenge the prevailing notion that adolescents are hypersensitive to reward and instead raise questions about the potential role of methodological factors on which rodent studies often differ.

Age and sex differences in behavioral flexibility, sensitivity to reward value, and risky decision-making

“…Despite evidence for a peri/post-pubertal peak in reward consumption (Friemel et al, 2010;Marshall et al, 2017), motivation (Friemel et al, 2010), and cocaine self-administration in males (Wong, Ford, Pagels, McCutcheon, & Marinelli, 2013), several studies measuring instrumental responding for non-drug reinforcers report either comparable responding (Sturman & Moghaddam, 2011;Kim, Simon, Wood, & Moghaddam, 2016;Naneix, Marchand, Di Scala, Pape, & Coutureau, 2012) or decreased responding in adolescents compared to adults (present study; Andrzejewski et al, 2011;Sturman et al, 2010;Hankosky et al, 2017). One factor that could contribute to the apparent discrepancies between reward consumption and instrumental responding is whether the measure accounts for differences in body weight.…”

“…Studies of reward consumption and drug self-administration adjust for differences in body weight, while measures of instrumental responding for non-drug reinforcers typically do not. As such, studies of sex differences in non-drug reward processing have found that females consume more reward per body weight when given ad libitum access (present study; Marshall et al, 2017;, but seem to respond for reinforcer similarly or more than males (present study; Hankosky et al, 2017) depending on whether the measure is normalized to body weight. In the present study, as the adolescents increase in body size across RI-30 sessions, they increase their responding in order to maintain their elevated reinforcement rate (adjusted for body weight) relative to adults.…”

“…Studies examining reward consumption normalized to body weight have consistently found that adolescent males consume more reward than their adult counterparts (Friemel et al, 2010) regardless of caloric content (Marshall et al, 2017). While these data suggest that adolescent reward hypersensitivity does not depend on age differences in caloric need, other studies that account for body weight but use non-caloric reinforcers do not clearly support this interpretation (Hankosky et al, 2017, Shram et al, 2008. Future studies are needed to understand how age differences in caloric need due to body size may influence instrumental responding.…”

“…Studies that utilize rodent models of adolescence, which have potential advantages for investigating underlying neural mechanisms of age differences in behavior, have typically focused on responses to psychoactive drugs (Kantak, Goodrich, & Uribe, 2007;Shahbazi, Moffett, Williams, & Frantz, 2008;Shram, Funk, Li, & Le, 2008;Anker & Carroll, 2010;Anker, Baron, Zlebnik, & Carroll, 2012;Hankosky, Westbrook, Haake, Marinelli, & Gulley, 2017).…”

Age- and sex-dependent effects of methamphetamine on cognitive flexibility and 5-HT2C receptor localization in the orbitofrontal cortex of Sprague-Dawley rats

“…Subjects were a total of 82 Sprague-Dawley rats (32 male, 50 female) that had previously been trained to self-administer d -methamphetamine HCl (0.08 mg/kg) or received non-contingent infusions of saline beginning during either adolescence or adulthood. The full methods outlining treatment of the METH rats used in this study and analysis of age- and sex-differences in METH self-administration was reported previously (Hankosky et al, 2018). Of the 46 rats that initiated METH self-administration, 15 males and 25 females met acquisition criteria to be included in this study.…”