RESUMO
RATIONALE: Nicotine promotes alcohol intake through pharmacological and behavioral interactions. As an example of the latter, nicotine can facilitate approach toward food- and alcohol-associated stimuli ("sign-tracking") in lever-Pavlovian conditioned approach (PavCA) paradigms. However, we recently reported that nicotine can also enhance approach toward locations of reward delivery ("goal-tracking") triggered by ethanol-predictive stimuli when the location of ethanol delivery is non-static (i.e., a retractable sipper bottle). OBJECTIVE: To determine whether the non-static nature of the reward location could have biased the development of goal-tracking in our previous study (Loney et al., 2019); we assessed the effect of nicotine in a lever-PavCA paradigm wherein the location of ethanol delivery was static (i.e., a stationary liquid receptacle). Then, to determine whether nicotine's enhancement of goal-tracking is unique to ethanol-predictive stimuli, we assessed the effect of systemic nicotine on approach triggered by food-predictive stimuli in a lever-PavCA paradigm. METHODS: Long-Evans rats were used in two PavCA experiments wherein a lever predicted the receipt of ethanol (15% vol/vol; experiment 1) or food (experiment 2) into a stationary receptacle. Prior to testing, rats were administered nicotine (0.4 mg/kg subcutaneously) or saline systemically. RESULTS: In both experiments, nicotine increased measures of goal-tracking, but not sign-tracking. CONCLUSION: Nicotine can facilitate approach to reward locations without facilitating approach to reward-predictive stimuli. As such, conceptualization of the mechanisms by which nicotine affects behavior must be expanded to explain an enhancement of goal-tracking by nicotine.
RESUMO
BACKGROUND: Nicotine and alcohol use are highly comorbid. Modulation of drug-paired extrinsic and intrinsic cues likely plays a role in this interaction, as cues can acquire motivational properties and augment drug seeking. The motivational properties of cues can be measured through Pavlovian conditioning paradigms, in which cues either elicit approach following pairing with the reinforcing properties of alcohol or elicit avoidance following pairing with the aversive consequences of alcohol. The present experiments tested whether nicotine would enhance the incentive properties of an appetitive ethanol (EtOH) cue and diminish the avoidance of an aversive EtOH cue in Pavlovian paradigms. METHODS: In experiment 1, male Long-Evans rats with or without prior chronic intermittent access to EtOH were administered nicotine or saline injections prior to Pavlovian conditioned approach (PavCA) sessions, during which conditioned approach to the cue ("sign-tracking") or the EtOH delivery location ("goal-tracking") was measured. In experiment 2, male Long-Evans rats were administered nicotine or saline injections prior to pairing a flavor cue with increasing doses of EtOH (i.p.) in an adaptation of the conditioned taste avoidance (CTA) paradigm. RESULTS: Results from PavCA indicate that, regardless of EtOH exposure, nicotine enhanced responding elicited by EtOH-paired cues with no effect on a similar cue not explicitly paired with EtOH. Furthermore, nicotine reduced sensitivity to EtOH-induced CTA, as indicated by a rightward shift in the dose-response curve of passively administered EtOH. The ED50 , or the dose of EtOH that produced a 50% reduction in intake relative to baseline, was significantly higher in nicotine-treated rats compared to saline-treated rats. CONCLUSIONS: We conclude that nicotine increases the approach and diminishes the avoidance elicited by Pavlovian cues paired, respectively, with the reinforcing and aversive properties of EtOH consumption in male rats. As such, nicotine may enhance alcoholism liability by engendering an attentional bias toward cues that predict the reinforcing outcomes of drinking.
