One-trial behavioral sensitization in preweanling rats: differential effects of cocaine, methamphetamine, methylphenidate, and d-amphetamine

Abstract

Rationale Preweanling rats exhibit robust one-trial cocaine-induced behavioral sensitization; however, it is uncertain whether other psychostimulants can also induce sensitization in young rats using the one-trial procedure. Objective The purpose of this study was to determine whether methamphetamine, methylphenidate, and D-amphetamine are capable of inducing one-trial locomotor sensitization in preweanling rats. Methods In a series of four experiments, rats were pretreated with cocaine (30 mg/kg), methamphetamine (2–12 mg/kg), methylphenidate (5–20 mg/kg), or amphetamine (5 mg/kg) before being placed in a novel activity chamber or the home cage on PD 19. Rats were then challenged with the same psychostimulant (20 mg/kg cocaine, 1–8 mg/kg methamphetamine, 2.5–7.5 mg/kg methylphenidate, or 1–2 mg/kg amphetamine) on PD 21, with distance traveled being measured for 180 min. In a separate experiment, rats were pretreated with methamphetamine on PD 16–19 and challenged with methamphetamine on PD 21. Results Only cocaine, but not various dose combinations of other psychostimulants, was able to produce one-trial behavioral sensitization in preweanling rats. Context-dependent locomotor sensitization was also evident if rats were pretreated with methamphetamine on PD 16–19 and tested on PD 21. Conclusions It is uncertain why only cocaine was able to induce one-trial locomotor sensitization in preweanling rats, but it is possible that: (a) the neural circuitry mediating sensitization differs according to psychostimulant, (b) cocaine is more readily associated with environmental contexts than other psychostimulants, or (c) affinity and pharmacokinetic factors may underlie cocaine’s ability to induce one-trial behavioral sensitization in preweanling rats.

Ontogeny of methamphetamine-induced and cocaine-induced one-trial behavioral sensitization in preweanling and adolescent rats

“…; Sobrian et al , 2003), while other ontogenetic effects are a consequence of programmed changes in the rats’ behavioral repertoire (Moody and Spear, 1992). In terms of this study, it was previously reported that methamphetamine does not induce one-trial behavioral sensitization during the late preweanling period (i.e., PD 19–21), whereas cocaine causes robust context-independent behavioral sensitization at the same age (McDougall et al, 2011a). Whether these two sets of findings are unique to the late preweanling period is unknown.…”

“…It was originally reported that methamphetamine would not support one-trial behavioral sensitization during the late preweanling period (i.e., on PD 21) (McDougall et al , 2011a). The present study greatly extends these findings by showing that rats will exhibit robust one-trial context-independent behavioral sensitization when methamphetamine is administered to younger age groups (PD 12–13 or PD 16–17).…”

“…In contrast, we recently reported that only cocaine, but not methamphetamine, amphetamine, or methylphenidate, causes one-trial behavioral sensitization on postnatal day (PD) 21 (McDougall et al ., 2011a). The inability of other psychostimulants to support one-trial sensitized responding was surprising, because all four compounds (cocaine, methamphetamine, amphetamine, and methylphenidate) induce multi-trial behavioral sensitization during the preweanling period (Duke et al ., 1997; Wood et al ., 1998; McDougall et al , 1999, 2011a; Tirelli, 2001). Various explanations can account for this psychostimulant-dependent effect.…”

Role of the D1 receptor for the dopamine agonist-induced one-trial behavioral sensitization of preweanling rats

“…In a series of studies, we previously reported that young rats show strong one-trial behavioral sensitization, but the age at which sensitized responding was exhibited depended on the psychostimulant being administered (McDougall et al 2011a, 2013; Kozanian et al 2012). For example, amphetamine and METH caused the most robust sensitized responding at PD 13 and PD 17, while cocaine only produced behavioral sensitization in older animals (i.e., at PD 21).…”

“…NPA has not been tested using this methodology, so a multi-dose parametric experiment was conducted to determine the early ontogeny of one-trial NPA-induced behavioral sensitization. The doses of cocaine and METH used in the present study were chosen because of their ability to produce strong one-trial behavioral sensitization in preweanling rats (McDougall et al 2007, 2011a; Herbert et al 2010). In all cases, lower doses of DA agonists were administered on the test day, relative to the pretreatment day, in order to preferentially induce locomotor activity rather than stereotypy (for a fuller discussion, see Robinson and Becker 1986).…”