Novel-object place conditioning in adolescent and adult male and female rats: effects of social isolation

Abstract

Elevated levels of novelty seeking are often seen during adolescence. Recent studies using a conditioned place preference (CPP) paradigm have shown that novelty may be rewarding for adult rats. The present study explored the impact of age, sex, and isolation stress on novelty seeking and novelty reward by assessing novel object-induced CPP in adolescent and adult male and female Sprague–Dawley rats housed either socially or in isolation. Responding to the novel objects during conditioning was higher in adolescent animals than adults, and was suppressed by social isolation only in adulthood, particularly among males. Novel object CPP was strong among adolescent males, whereas only socially isolated adult males demonstrated preference for the compartment paired with the novel objects. This age difference was not evident in females, with both adolescent and adult group-housed females, but not their isolated counterparts, showing novel-object place conditioning. These dissociations between novelty-directed behaviors during conditioning and novelty reward in the CPP paradigm support the suggestion that mechanisms underlying novelty seeking are separable from those involved in the rewarding effects of novelty. High levels of novelty seeking demonstrated by adolescents do not necessarily predict high rewarding properties of novelty, with the latter also being influenced by environmental and gender-related factors.

Introduction

Relative to adults and children, human adolescents exhibit an increased level of risk-taking behavior, associated with the motivation to experience multiple new and intense stimuli to attain potential rewards [1], [2]. The motivation to seek out new experiences, i.e., novelty seeking behavior, has been identified as a significant contributor to current and future drug use, multiple drug use, and later abuse [3], [4], [5], [6].

Given that adolescence is a time of acquiring new skills for survival away from parents, enhanced novelty seeking may have been evolutionally conserved for its adaptive value during this developmental period, contributing to exploration of novel areas and providing the opportunity to find new sources of food, water, and mates (see Ref. [7]). Although little explored to date, there is some experimental evidence that age may play a role in responding to novelty, with adolescent rodents being more responsive to novel stimuli than their adult counterparts. For instance, adolescent mice spent more time in a novel environment and had higher levels of novelty-induced activity than adults [8]. In a similar way, adolescent rats have been reported to be more active and to engage in more exploratory behaviors in novel situations than adults [9], [10].

Responding to novelty may also be influenced by social factors. In humans, a number of social variables, including social conformity, peer deviance, and social support influence novelty seeking behavior in adolescence [11]. Likewise, the presence of peers before testing enhanced responding to novelty in nonhuman primates, increasing exploration of novel objects relative to their socially deprived counterparts [12]. In contrast, rats reared in social isolation were more responsive to novelty relative to rats housed socially (see Ref. [13] for references and review), as indexed by increased locomotor activity [14], [15], enhanced preference for novel environments [16], and elevated levels of object exploration [17]. Such isolation-induced increases in object exploration were found to be age-specific, emerging only in animals socially deprived between 25 and 45 days of age and not by isolation initiated after P45 [18]. These findings suggest that responding to novelty of adolescent animals may be influenced by social factors in a way different from that of their adult counterparts.

Conditioned place preference (CPP), a widely used behavioral paradigm to measure drug reward in laboratory animals, has been employed recently for assessment of the rewarding properties of novel environmental stimuli. In these studies, socially isolated adult male rats received access to novel objects in one distinct environment (e.g., one compartment of a CPP apparatus containing distinct tactile and visual cues), while receiving exposure to a second distinct environment (the other compartment of the apparatus) in the absence of any novel objects. In a choice test, when exposed to the entire apparatus without novel objects, rats showed preference for the environment that had been previously paired with novelty [19], [20], [21]. Novelty of the objects is an important issue in this paradigm, since animals that received access to familiar objects in one of the compartments of the CPP apparatus did not show preference for that environment later on, and during conditioning they spent significantly less time interacting with the familiar object than their counterparts exposed to novel objects [21]. These results suggest that access to novel but not familiar objects is rewarding, findings that validate the use of this procedure for the assessment of novelty reward.

There are no reports as to whether novel stimuli would support place preference conditioning in adolescent animals, nor whether such conditioning would be influenced by sex and housing conditions in an age-specific manner. Therefore, the main objective of the present study was to evaluate how age, sex, and isolate housing influence the rewarding properties of novelty using the novel-object place conditioning paradigm developed by Bevins and Bardo [20].