Importance of environmental context for one- and three-trial cocaine-induced behavioral sensitization in preweanling rats

Abstract

Rationale-Preweanling rats, unlike adults, exhibit context-independent behavioral sensitization after a single pretreatment injection of cocaine.Objective-The purpose of this study was to examine environmental factors modulating one-and three-trial sensitization in preweanling rats.Methods-For preweanling rats, drug pretreatments occurred on PD 17-PD 19 (Experiment 1) or PD 19 (Experiment 2). One set of rats was injected with cocaine (30 mg/kg) and placed in anesthesia ("small"), operant conditioning ("large"), or activity chambers for 30 min. Rats were returned to the home cage and injected with saline. Additional groups of rats were injected with saline and placed in small, large, or activity chambers for 30 min and then injected with cocaine after being returned to the home cage. Control groups were injected with saline at both time points. In separate experiments, rats were pretreated with cocaine or saline and restricted to the home cage. On PD 20, all rats were injected with cocaine (20 mg/kg) and placed in activity chambers where locomotor activity was assessed for 60 min. For comparison purposes, sensitization was also assessed in adult rats.Results-Adult male and female rats exhibited only context-dependent sensitization, whereas preweanling rats showed context-independent sensitization in a variety of conditions (e.g., when pretreated with cocaine in various novel chambers or the home cage).Conclusions-These results suggest that nonassociative mechanisms underlying behavioral sensitization are functionally mature in preweanling rats, but associative processes modulating the strength of the sensitized response do not function in an adult-like manner during the preweanling period.

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

“…It is uncertain why D1 receptor antagonism is only able to disrupt the one-trial cocaine sensitization of adult rodents, although the context-dependent nature of one-trial sensitization may be critical. Because drug-environment associations are unimportant for the one-trial behavioral sensitization of preweanling rats (McDougall et al 2009b, 2011b; Herbert et al 2010), we originally hypothesized that SCH23390 would not attenuate cocaine-induced sensitized responding on PD 21. This result was obtained.…”

“…Accumulating evidence also indicates that the mechanisms mediating one-trial behavioral sensitization vary markedly between the preweanling period and adulthood. For example, there is abundant evidence that contextual conditioning does not influence the one-trial behavioral sensitization of preweanling rats (e.g., McDougall et al 2009b), whereas drug-environment associations are necessary for the occurrence of one-trial behavioral sensitization in older animals (e.g., Weiss et al 1989). In adult rats, the D1 antagonist SCH23390 blocks the induction of one-trial cocaine-induced behavioral sensitization, as well as METH- and apomorphine-induced sensitized responding (Mattingly et al 1991; Kuribara 1995b; Valjent et al 2010).…”

“…Similar to adults, the multi-trial behavioral sensitization of preweanling rats is influenced by associative processes, because sensitized responding is more persistent if drug pretreatment and testing occur in the same environmental context (Wood et al 1998; Zavala et al 2000). In contrast to adult rats, however, the one-trial behavioral sensitization of preweanling rats is context-independent, since the sensitized responding of young rats is equally robust if drug pretreatment occurs in the test chamber, home cage, or a separate novel compartment (McDougall et al 2009b, 2011b; Herbert et al 2010). In preweanling rats, the context-independent nature of one-trial behavioral sensitization has been shown using cocaine, amphetamine, and METH (Kozanian et al 2012; McDougall et al 2013).…”

Effects of D2 or combined D1/D2 receptor antagonism on the methamphetamine-induced one-trial and multi-trial behavioral sensitization of preweanling rats

“…Most importantly, the sensitized responding of preweanling rats appears to be weaker and less persistent than in older animals (Smith and Morrell 2008; McDougall et al 2009b). As with adults, the multi-trial behavioral sensitization of preweanling rats is stronger if drug pretreatment and testing occur in the same environmental context (i.e., context-dependent sensitization) (Wood et al 1998; Zavala et al 2000).…”

“…As with adults, the multi-trial behavioral sensitization of preweanling rats is stronger if drug pretreatment and testing occur in the same environmental context (i.e., context-dependent sensitization) (Wood et al 1998; Zavala et al 2000). Unlike adults, however, the one-trial behavioral sensitization of preweanling rats is context-independent (McDougall et al 2009b; Herbert et al 2010; Kozanian et al 2012); whereas, the one-trial behavioral sensitization of adult rats is completely context-dependent (Weiss et al 1989; Jackson and Nutt 1993; Battisti et al 1999a, b). The relative importance of associative learning processes may explain why adult rats show a sensitized response for many months after a single exposure to a psychostimulant (Leith and Kuczenski 1982; Robinson et al 1982; Valjent et al 2010), while the one-trial behavioral sensitization of preweanling rats persists for only a few days (McDougall et al 2009a).…”