Repeated nicotine exposure during adolescence alters reward-related learning in male and female rats

Abstract

Rationale Repeated nicotine exposure causes neuroadaptations in limbic cortico-striatal circuits involved in learning and motivation. Such alterations are relevant to addiction because they are suggested to mediate the ability of smoking-associated stimuli to control behavior and to enhance nicotine-seeking and -taking behaviors. Female smokers report higher cue reactivity relative to their male counter parts, yet little is known about putative gender-specific effects of adolescent nicotine exposure on reward-related learning. Prior repeated nicotine exposure in adult male rats enhances Pavlovian approach behavior and conditioned reinforcement Objective Given that smoking is typically initiated during adolescence, here we assessed the extent to which adolescent nicotine exposure impacts Pavlovian approach and conditioned reinforcement in male and female rats. Methods Rats were injected with nicotine on postnatal days 31–45 prior to training on Pavlovian approach behavior starting on day 51. They were trained to associate a conditioned stimulus (CS), illumination of a magazine light, and tone, with an unconditioned stimulus (US), the delivery of water, for 10-daily sessions, and then were tested on the acquisition of responding with conditioned reinforcement. Results Adolescent nicotine exposure selectively increased approach to the magazine during the CS in males but decreased approach to the magazine during the CS in female rats. Vehicle-exposed female rats, however, showed greater magazine approach during the CS than did male control rats. Prior nicotine exposure also enhanced conditioned reinforcement in both male and female rats. Conclusions Repeated exposure to nicotine during adolescence had opposite effects on Pavlovian approach behavior in male and female rats but produced enhancement of increases in acquisition of a new response with conditioned reinforcement. Novel information on how nicotine exposure influences reward-related learning during adolescence may increase our understanding of neurobiological mechanisms involved in the initiation of smoking behavior.

Chronic Nicotine Exposure Initiated in Adolescence and Unpaired to Behavioral Context Fails to Enhance Sweetened Ethanol Seeking

“…As exposure to nicotine during adolescence has been shown to increase responding for conditioned reinforcers when compared to saline-exposed animals (Quick et al, 2014 ), we measured reinstatement of reward seeking after exposure to reward-associated cues. Reinstatement of operant responding for the cues previously associated with sweetened ethanol was measured in a single extinction-reinstatement session.…”

“…However, in adolescence the sex difference is less clear, as some studies found that males drank more ethanol than females (e.g., Vetter-O’Hagen et al, 2009 ) and others found more drinking in females (e.g., Varlinskaya et al, 2015 ). When administered only during adolescence, nicotine enhanced conditioned reinforcement in both male and female adults, but increased Pavlovian conditioned approach only in adult males (Quick et al, 2014 ). Thus, it is possible that nicotine would have different effects in males under the current study design, which may be addressed by future studies.…”

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.…”

Paradoxical effects of injection stress and nicotine exposure experienced during adolescence on learning in a serial multiple choice (SMC) task in adult female rats

“…Very few indications are given by experimenters as to why one procedure is chosen over another. However, all of the foregoing methods of adolescent nicotine exposure in rats have been shown to cause neural and behavioral changes that last into adulthood (Abreu-Villaça et al, 2003a; Abreu-Villaça et al, 2003b; Adriani, Spijker, Deroche-Gamonet, Laviola, Le Moal, Smit, & Piazza, 2003; Barron, White, Swartzwelder, Bell, Rodd, Slawecki, Ehlers, Levin, Rezvani, & Spear, 2005; Belluzzi, Lee, Oliff, & Leslie, 2004; Brielmaier, McDonald, & Smith, 2007; Counotte et al, 2009; Dwyer, McQuown, & Leslie, 2009; Fountain et al, 2008; McDonald, Dailey, Bergstrom, Wheeler, Eppolito, Smith, & Smith, 2005; Natividad, Torres, Friedman, & O'Dell, 2013; Philpot, Engberg, & Wecker, 2014; Pickens et al, 2013; Polesskaya, Fryxell, Merchant, Locklear, Ker, McDonald, Eppolito, Smith, Wheeler, & Smith, 2007; Quick, Olausson, Addy, & Taylor, 2014; Schochet et al, 2004; Slawecki et al, 2004; Slotkin, 2002; Slotkin, Bodwell, Ryde, & Seidler, 2008; Slotkin, MacKillop, Rudder, Ryde, Tate, & Seidler, 2007; Spaeth et al, 2010; Trauth, McCook, Seidler, & Slotkin, 2000; Trauth, Seidler, McCook, & Slotkin, 1999; Trauth, Seidler, & Slotkin, 2000a, 2000b; Wheeler, Smith, Bachus, McDonald, Fryxell, & Smith, 2013). Furthermore, recent research has found that various forms of stress in adolescence can have long-term effects on cognition (Green & McCormick, 2013; Isgor, Kabbaj, Akil, & Watson, 2004; Morrissey, Mathews, & McCormick, 2011; Torregrossa, Xie, & Taylor, 2012).…”