Differential effects of methamphetamine and cocaine on conditioned place preference and locomotor activity in adult and adolescent male rats

Abstract

SummaryHuman and animal laboratory studies show that adolescents and adults respond differently to drugs and that drug administration during adolescence leads to different behavioral effects than during adulthood. Although there are a number of studies on the effects of cocaine, little is known about the effects of methamphetamine in adolescent vs adult rats. In the present study, sensitivity to the conditioned reward of multiple doses of methamphetamine or cocaine was evaluated in male adolescent (PND 34) and adult (PND 66) rats using a conditioned place preference (CPP) paradigm. In addition, the locomotor-activating effects of methamphetamine were determined across a five-day period of administration. After three days of training with cocaine, both adolescent and adult male rats developed CPP to cocaine, however, the dose-effect curve for cocaine CPP was shifted to the left in adolescent compared to adult rats. In contrast to the development of CPP to cocaine in both groups after three days of conditioning, methamphetamine CPP occurred only in adolescent, and not in adult rats. After five days of training, however, both adolescent and adult rats exhibited identical responses to multiple doses of methamphetamine and a significant CPP was observed in both groups. Daily administration of methamphetamine increased locomotor activity in both adolescent and adult rats, with a greater effect seen in the adults. In neither group, was there evidence of a significant sensitization to the locomotor-activating effects of methamphetamine. These data show that adolescents are more sensitive to psychostimulant reward and thus to the conditioned rewarding properties of cocaine or methamphetamine than adults. A better understanding of this difference may lead to age-specific preventions and treatments for psychostimulant abuse.

Comparative Behavioral Pharmacology of Three Pyrrolidine-Containing Synthetic Cathinone Derivatives

“…The doseeffect curves for a-PBP and a-PVP were both inverted U-shaped functions, with the low and high doses not producing conditioned place preference. Similar inverted U dose-effect functions have been reported for conditioned place preference with other psychostimulants such as amphetamine, cocaine, and methamphetamine (Adriani and Laviola, 2003;RodriguezAlarcòn et al, 2007;Zakharova et al, 2009). Other cathinones also produce reward and reinforcement.…”

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

“…Although there is evidence for adolescent reduced sensitivity to the reinforcing properties of opiate drugs (Doherty et al 2013;Doherty and Frantz 2012;MayerBlackwell et al 2014;Niikura et al 2013), the existing research on age-dependent differences in the reinforcing and locomotor-activating effects of psychostimulants is equivocal. Studies have shown that adolescents are more sensitive (Zakharova et al 2009;Mathews et al 2011), less sensitive Mathews and McCormick 2007;Zakharova et al 2009), or no different (Mathews and McCormick, 2007) than their adult counterparts. One possibility is that age differences in pharmacokinetics could account for reduced sensitivity to METH in adolescents, but findings are again mixed.…”

Adolescent rats fail to demonstrate a LiCl-induced pre-exposure effect: Implications for the balance of drug reward and aversion in adolescence

“…As noted, adolescents display weaker taste avoidance conditioning in general, and this, too, could be a function of poorer learning in this group. Although possible, adolescents actually display greater drug-induced place preferences (see Badanich et al, 2006;Belluzzi et al, 2004;Brenhouse & Andersen, 2008;Douglas et al, 2003;Torres et al, 2008;Vastola et al, 2002;Zakharova et al, 2009), suggesting that learning in general is not impaired in adolescents. While it is possible that there is a selective learning deficit associated with aversive conditioning (including taste avoidance learning), classic fear conditioning work predicated upon contextual learning suggests that age does not influence the acquisition or extinction of conditioning (Denenberg & Kline, 1958;Kirby, 1963), Interestingly, the retention of such avoidance responses does display a U-shaped function of age (Denenberg & Kline, 1958;Kirby, 1963;Campbell & Campbell, 1962), suggesting that retention of such learning is age dependent.…”