The tendency to sign-track predicts cue-induced reinstatement during nicotine self-administration, and is enhanced by nicotine but not ethanol

Versaggi, Cassandra L.; King, Christopher P.; Meyer, Paul J.

doi:10.1007/s00213-016-4341-7

Cited by 54 publications

(56 citation statements)

References 72 publications

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“…Our model produced sign- and goal-tracking behavior similar to previous reports (Flagel et al, 2009; Palmatier et al, 2013b; Versaggi et al, 2016), as control animals exhibited individual preferences for the sign- or goal-tracking behavior. In addition, nicotine exposure increased the likelihood that an animal would display a sign-tracking response in Experiments 1 and 2.…”

Section: Discussionsupporting

confidence: 82%

“…Sign tracking has recently come under increasing scrutiny in substance dependence research because of its association with drug abuse vulnerability (Saunders and Robinson, 2013; Tomie et al, 2008). Although both sign and goal tracking rely on the same mesotelencephalic systems implicated in substance dependence (Flagel et al, 2011b; Saunders and Robinson, 2012), individual subjects who display a greater propensity to sign track show increased drug self-administration (Saunders and Robinson, 2011; Versaggi et al, 2016). These individual differences are also linked to variation in stress responses, neurotransmitter release, and neuronal activation in areas including the PFC and the nucleus accumbens (Saunders and Robinson, 2013; Tomie et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies from multiple laboratories suggest a special relationship between the effects of nicotine and approach to incentives (Palmatier et al, 2014; Versaggi et al, 2016; Yager and Robinson, 2015). The interaction between nicotine and incentives is especially relevant to tobacco use and dependence because preclinical studies have repeatedly demonstrated that nicotine is a weak primary reinforcer (Foll and Goldberg, 2009; Palmatier et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Orbitofrontal participation in sign- and goal-tracking conditioned responses: Effects of nicotine

et al. 2017

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Pavlovian conditioned stimuli can acquire incentive motivational properties, and this phenomenon can be measured in animals using Pavlovian conditioned approach behavior. Drugs of abuse can influence the expression of this behavior, and nicotine in particular exhibits incentive amplifying effects. Both conditioned approach behavior and drug abuse rely on overlapping corticolimbic circuitry. We hypothesize that the orbitofrontal cortex (OFC) regulates conditioned approach, and that one site of nicotine action is in the OFC where it reduces cortical output. To test this, we repeatedly exposed rats to 0.4 mg/kg nicotine (s.c.) during training and then pharmacologically inactivated the lateral OFC or performed in vivo electrophysiological recordings of lateral OFC neurons in the presence or absence of nicotine. In Experiment 1, animals were trained in a Pavlovian conditioning paradigm and behavior was evaluated after inactivation of the OFC by microinfusion of the GABA agonists baclofen and muscimol. In Experiment 2, we monitored phasic firing of OFC neurons during Pavlovian conditioning sessions. Nicotine reliably enhanced conditioned responding to the conditioned cue, and inactivation of the OFC reduced conditioned responding, especially the sign-tracking response. OFC neurons exhibited phasic excitations to cue presentation and during goal tracking, and nicotine acutely blunted this phasic neuronal firing. When nicotine was withheld, both conditioned responding and phasic firing in the OFC returned to the level of controls. These results suggest that the OFC is recruited for the expression of conditioned responses, and that nicotine acutely influences this behavior by reducing phasic firing in the OFC.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Orbitofrontal participation in sign- and goal-tracking conditioned responses: Effects of nicotine

et al. 2017

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“…This task assesses sensitivity to cues in the environment, by measuring the ability of those cues to elicit approach behavior (Meyer et al , 2012a, Robinson et al , 2014). Response to Pavlovian reward cues have been further associated with response to drug-cues (Saunders & Robinson, 2010, Versaggi et al , 2016) and action impulsivity (King et al , 2016, Lovic et al , 2011). Response to environmental cues may explain one mechanism by which drug-associated stimuli come to prompt maladaptive behavior or drug seeking (Childress et al , 2008, Franklin et al , 2011).…”

Section: Discussionmentioning

confidence: 99%

Cdh13 and AdipoQ gene knockout alter instrumental and Pavlovian drug conditioning

King

Militello

Hart

et al. 2017

Genes Brain and Behavior

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Genome-wide association studies in humans have suggested that variants of the cadherin-13 (CDH13) gene are associated with substance use disorder, subjective response to amphetamine, and attention deficit hyperactivity disorder. To examine the role of the Cdh13 and its peptide ligand adiponectin (AdipoQ) in addiction-related behaviors, we assessed Cdh13 knock-out rats and AdipoQ knock-out mice using intravenous cocaine self-administration and conditioned place preference paradigms. During intravenous cocaine self-administration, male Cdh13 heterozygous (+/−) and knock-out (−/−) rats showed increased cue-induced reinstatement compared to wild-type rats when presented with a cocaine-paired stimulus, whereas female Cdh13 rats showed no differences across genotype. Cdh13 −/− rats showed higher responding for a saccharin reinforcer and learned the choice reaction time task more slowly than wild-types. However, we found no differences between Cdh13 −/− and +/+ rats in responding for sensory reinforcement, number of premature responses in the reaction time task, tendency to approach a Pavlovian food cue, conditioned place preference and locomotor activation to cocaine (10 or 20 mg/kg). In AdipoQ −/− mice there was a significant increase in conditioned place preference to methamphetamine (1 mg/kg) but not to a range of d-amphetamine doses (0.5, 1, 2 and 4 mg/kg). Taken together, these data suggest that Cdh13 and AdipoQ regulate sensitivity to psychomotor stimulants and palatable rewards without producing major changes in other behaviors. In humans, these two genes may regulate sensitivity to natural and drug rewards, thus influencing susceptibility to the conditioned drug effects and relapse.

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“…Previous work has shown that tendency to sign-track a food cue is associated with different patterns of drug-related behavior, including higher progressive ratio break-points during cocaine self-administration, more robust cocaine and nicotine cue-induced reinstatement, and stronger cocaine conditioned place preference (Meyer et al 2012b; Saunders and Robinson 2010; 2011; Versaggi et al 2016; Yager and Robinson 2013). For this reason, sign-tracking is considered a model for drug-cue responsivity, in that individuals displaying this behavior may be more vulnerable to the effects of cues on relapse to drug-taking (Flagel et al 2009; Saunders and Robinson 2013).…”

Section: Introductionmentioning

confidence: 99%

Individual differences in food cue responsivity are associated with acute and repeated cocaine-induced vocalizations, but not cue-induced vocalizations

2016

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Rationale Individuals prone to attribute incentive salience to food-associated stimuli (“cues”) are also more sensitive to cues during drug-seeking and drug-taking. This may be due in part to a difference in sensitivity to the affective or other stimulus properties of the drug. In rats, these properties are associated with 50 kHz ultrasonic vocalizations (USVs), in that they are elicited during putative positive affective and motivational states, including in response to drugs of abuse. Objectives We sought to determine whether individual differences in the tendency to attribute incentive salience to a food cue (as measured by approach) were associated with differences in cocaine-induced USVs. We also tested whether the food cue would elicit USVs, and if this response was related to approach to the food cue. Methods In experiment 1, rats underwent Pavlovian Conditioned Approach (PavCA) training where they learned to associate a cue (an illuminated lever) with the delivery of a food pellet into a food cup. Subjects were categorized based on their approach to the cue (“sign-trackers”), or to the food cup (“goal-trackers”). Rats subsequently underwent nine testing days in which they were given saline or cocaine (10 mg/kg i.p), and placed into a locomotor chamber. In experiment 2, rats were first tested in the locomotor chambers for one saline-treated day followed by one cocaine-treated day, and then trained in PavCA. USVs were recorded from a subset of individuals during the last day of PavCA to determine if the food cue would elicit USVs. Results Sign-trackers produced 5 - 24 times more cocaine-induced 50 kHz USVs compared to goal-trackers for all days of experiment 1, and this response sensitized with repeated cocaine, only in sign-trackers. Similarly in experiment 2, individuals that produced the most cocaine-induced USVs on a single exposure also showed the greatest tendency to sign-track during PavCA. Lastly, while sign-trackers produced more USVs during PavCA generally, the cue itself did not elicit additional USVs in sign- or goal-trackers. Conclusions These results indicate a robust and consistent relationship between approach to a food cue and cocaine-induced USV production. Thus, these USVs may index the neurobiological differences underlying the behavioral distinctions of sign- and goal-trackers.

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The tendency to sign-track predicts cue-induced reinstatement during nicotine self-administration, and is enhanced by nicotine but not ethanol

Cited by 54 publications

References 72 publications

Orbitofrontal participation in sign- and goal-tracking conditioned responses: Effects of nicotine

Orbitofrontal participation in sign- and goal-tracking conditioned responses: Effects of nicotine

Cdh13 and AdipoQ gene knockout alter instrumental and Pavlovian drug conditioning

Individual differences in food cue responsivity are associated with acute and repeated cocaine-induced vocalizations, but not cue-induced vocalizations

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