Amphetamine-induced incentive sensitization of sign-tracking behavior in adolescent and adult female rats.

Abstract

Age-specific behavioral and neural characteristics may predispose adolescents to initiate and escalate use of alcohol and drugs. Adolescents may avidly seek novel experiences, including drugs of abuse, because of enhanced incentive motivation for drugs and natural rewards, perhaps especially when that incentive motivation is sensitized by prior drug exposure. Using a Pavlovian conditioned approach (PCA) procedure, sign-tracking (ST) and goal-tracking (GT) behavior was examined in amphetamine-sensitized and control adolescent and adult female Sprague-Dawley rats, with expression of elevated ST behavior used to index enhanced incentive motivation for reward-associated cues. Rats were first exposed to a sensitizing regimen of amphetamine injections (3.0 mg/kg/ml d-amphetamine per day) or given saline (0.9% w/v) once daily for 4 days. Expression of ST and GT was then examined over 8 days of PCA training consisting of 25 pairings of an 8-sec presentation of an illuminated lever immediately followed by responseindependent delivery of a banana-flavored food pellet. Results showed that adults clearly displayed more ST behavior than adolescents, reflected via both more contacts with, and shorter latencies to approach, the lever. Prior amphetamine sensitization increased ST (but not GT) behaviors regardless of age. Thus, when indexed via ST, incentive motivation was found to be greater in adults than adolescents, with a prior history of amphetamine exposure generally sensitizing incentive motivation for cues predicting a food reward regardless of age. Keywords adolescent; amphetamine; sign-tracking; incentive sensitization; rats Adolescents differ from individuals at other ages in the way they respond to and interact with natural rewards and drugs, exhibiting age-related increases in social behavior, noveltyseeking/risk-taking and consummatory behaviors. It is also during adolescence that most drug users have their first drug-related experiences, with almost 50% of high school seniors reporting use of an illicit drug during their lifetime (Johnston, O'Malley, Bachman, & Schulenberg, 2010). Given ethical constraints regarding research that can be conducted with human youth, animal models provide an important tool for researchers to investigate factors

Adolescent cocaine exposure enhances goal-tracking behavior and impairs hippocampal cell genesis selectively in adult bred low-responder rats

“…Given that bLRs and bHRs are known to differ in these behaviors, the effects of adolescent cocaine treatment on Pavlovian conditioned approach behavior were analyzed separately within each phenotype. Contrary to what we initially hypothesized based, in part, on previous findings (Doremus-Fitzwater and Spear 2011; McClory and Spear 2014; Saddoris et al 2016), bLR rats exposed to cocaine during adolescence did not acquire a sign-tracking response as measured by the number of lever-CS contacts, probability to approach the lever-CS, and latency to contact the lever-CS (Fig. 4 a–c).…”

“…Others have previously shown that exposure to drugs of abuse (i.e., amphetamine, ethanol) in adolescence enhances the tendency to sign-track in outbred rats (Doremus-Fitzwater and Spear 2011; McClory and Spear 2014), and similar increases in sign-tracking behavior were reported in adult rats after cocaine self-administration (Saddoris et al 2016). The seemingly discrepant results reported here are likely due to the use of selectively-bred bLR rats, which, unlike outbred rats, have an inherent predisposition towards goal-tracking behavior (Flagel et al 2010), amongst other inborn traits (Flagel et al 2014).…”

“…Previous studies in outbred rats have shown that exposure to ethanol during adolescence (McClory and Spear 2014) increases sign-tracking behavior, as does exposure to psychostimulants either during adolescence (Doremus-Fitzwater and Spear 2011) or in adulthood (Saddoris et al 2016). While the specific neurobiological mechanisms underlying these drug-induced effects on sign-tracking behavior have not been elucidated, dopaminergic transmission in the NAc core is likely involved (Saddoris et al, 2016), as it has been shown to play a critical role in the sign-tracking, but not the goal-tracking response (Flagel et al 2011; Saunders and Robinson 2012; Yager et al 2014).…”

Adolescent Alcohol Exposure Amplifies the Incentive Value of Reward-Predictive Cues Through Potentiation of Phasic Dopamine Signaling

“…A second potential limitation to the interpretation of the current results is the extent to which the findings are selective to alcohol exposure in adolescence. Previous studies have investigated the effect of nicotine and amphetamine exposure during adolescence on Pavlovian conditioned approach behavior in adulthood (Quick et al, 2014;Doremus-Fitzwater and Spear, 2011). Adolescent nicotine exposure (on PND 31-45) was shown to increase approach to a CS in male animals, whereas approaches to the CS were reduced in females.…”

Effects of ethanol exposure during adolescence or in adulthood on Pavlovian conditioned approach in Sprague-Dawley rats

“…Emergence of ST is thought to reflect the motivational property of the reward, and has the potential to develop into “pathological” incentive salience (Flagel, Akil, & Robinson, 2009; Robinson & Berridge, 2003). Sign tracking has also been linked to addiction-like behaviors (Tomie, Grimes, & Pohorecky, 2008) and can be induced by drugs of abuse (Doremus-Fitzwater & Spear, 2011; Uslaner, Acerbo, Jones, & Robinson, 2006). Our lab has previously shown that sign tracking in the PCA task seen in adulthood is sensitive to adolescent stress exposure (Anderson & Spear, 2011).…”