scholarly journals Variation in the Form of Pavlovian Conditioned Approach Behavior among Outbred Male Sprague-Dawley Rats from Different Vendors and Colonies: Sign-Tracking vs. Goal-Tracking

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e75042 ◽  
Author(s):  
Christopher J. Fitzpatrick ◽  
Shyam Gopalakrishnan ◽  
Elizabeth S. Cogan ◽  
Lindsay M. Yager ◽  
Paul J. Meyer ◽  
...  
2018 ◽  
Author(s):  
Alexander F. Gileta ◽  
Christopher J. Fitzpatrick ◽  
Apurva S. Chitre ◽  
Celine L. St. Pierre ◽  
Elizabeth V. Joyce ◽  
...  

AbstractSprague Dawley (SD) rats are one of the most commonly used outbred rat strains. Despite this, the genetic characteristics of SD are poorly understood. We collected behavioral data from 4,625 SD rats acquired predominantly from two commercial vendors, Charles River Laboratories and Harlan Sprague Dawley Inc. Using double-digest genotyping-by-sequencing (ddGBS), we obtained dense, high-quality genotypes at 234,887 SNPs across 4,061 rats. This genetic data allowed us to characterize the variation present in Charles River vs. Harlan SD rats. We found that the two populations are highly diverged (FST > 0.4). We also used these data to perform a genome-wide association study (GWAS) of Pavlovian conditioned approach (PavCA), which assesses the propensity for rats to attribute motivational value to discrete, reward-associated cues. Due to the genetic divergence between rats from Charles River and Harlan, we performed two separate GWAS by fitting a linear mixed model that accounted for within vendor population structure and using meta-analysis to jointly analyze the two studies. We identified 18 independent loci that were significantly associated with one or more metrics used to describe PavCA; we also identified 3 loci that were body weight, which was only measured in a subset of the rats. The genetic characterization of SD rats is a valuable resource for the rat community that can be used to inform future study design.Author SummaryOutbred Sprague Dawley rats are among the most commonly used rats for neuroscience, physiology and pharmacological research. SD rats are sold by several commercial vendors, including Charles River Laboratories and Harlan Sprague Dawley Inc. (now Envigo). Despite their wide spread use, little is known about the genetic diversity of SD. We genotyped more than 4,000 SD rats, which we used to characterize genetic differences between SD rats from Charles River Laboratories and Harlan. Our analysis revealed that the two SD colonies are highly divergent. We also performed a genome-wide association study (GWAS) for Pavlovian conditioned approach (PavCA), which assesses the propensity for rats to attribute motivational value to discrete, reward-associated cues. Our results demonstrate that, despite sharing an identical name, SD rats are obtained from different vendors are genetically very different. We conclude that results obtained using SD rats should not be presented without also carefully noting the vendor.


2019 ◽  
Author(s):  
Ali Gheidi ◽  
Lora M. Cope ◽  
Christopher J. Fitzpatrick ◽  
Benjamin N. Froehlich ◽  
Rachel Atkinson ◽  
...  

AbstractPavlovian conditioned approach paradigms are used to characterize the nature of motivational behaviors in response to stimuli as either directed toward the cue (i.e., sign-tracking) or the site of reward delivery (i.e., goal-tracking). Recent evidence has shown that activity of the endocannabinoid system increases dopaminergic activity in the mesocorticolimbic system, and other studies have shown that sign-tracking behaviors are dependent on dopamine. Therefore, we hypothesized that administration of a cannabinoid agonist would increase sign-tracking and decrease goal-tracking behaviors. Forty-seven adult male Sprague Dawley rats were given a low, medium, or high dose of the cannabinoid agonist CP-55,940 (N=12 per group) or saline (N=11) before Pavlovian conditioned approach training. A separate group of rats (N=32) were sacrificed after PCA training for measurement of cannabinoid receptor type 1 (CB1) and fatty acid amide hydrolase (FAAH) using in situ hybridization. Contrary to our initial hypothesis, CP-55,940 dose-dependently decreased sign-tracking and increased goal-tracking behavior. CB1 expression was higher in sign-trackers compared to goal-trackers in the prelimbic cortex, but there were no significant differences in CB1 or FAAH expression in the infralimbic cortex, dCA1, dCA3, dorsal dentate gyrus, or amygdala. These results demonstrate that cannabinoid signaling can specifically influence behavioral biases toward sign- or goal-tracking. Pre-existing differences in CB1 expression patterns, particularly in the prelimbic cortex, could contribute to individual differences in the tendency to attribute incentive salience to reward cues.


2012 ◽  
Vol 226 (2) ◽  
pp. 247-259 ◽  
Author(s):  
Matthew I. Palmatier ◽  
Kimberley R. Marks ◽  
Scott A. Jones ◽  
Kyle S. Freeman ◽  
Kevin M. Wissman ◽  
...  

2021 ◽  
Vol 15 ◽  
Author(s):  
Hailley Angelyn ◽  
Gregory C. Loney ◽  
Paul J. Meyer

RationaleNicotine 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).ObjectiveTo 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.MethodsLong–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.ResultsIn both experiments, nicotine increased measures of goal-tracking, but not sign-tracking.ConclusionNicotine 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.


2020 ◽  
Author(s):  
Joshua L Haight ◽  
Paolo Campus ◽  
Cristina E Maria-Rios ◽  
Allison M Johnson ◽  
Marin S Klumpner ◽  
...  

AbstractRationalePrior research suggests that inputs from the lateral hypothalamic area (LHA) to the paraventricular nucleus of the thalamus (PVT) contribute to the attribution of incentive salience to Pavlovian-conditioned reward cues. However, a causal role for the LHA in this phenomenon has not been demonstrated. In addition, it is unknown which hypothalamic neurotransmitter or peptide system(s) are involved in mediating incentive salience attribution.ObjectivesTo examine: 1) the role of the LHA in the propensity to attribute incentive salience to reward cues, and 2) the role of orexinergic signaling in the PVT on the expression of Pavlovian conditioned approach (PavCA) behavior, a reflection of incentive salience attribution.MethodsMale Sprague-Dawley rats received bilateral excitotoxic lesions of the LHA prior to the acquisition of Pavlovian conditioned approach (PavCA) behavior. A separate cohort of male rats acquired PavCA behavior and were characterized as sign-trackers (STs) or goal-trackers (GTs) based on their conditioned response. The orexin 1 receptor (OX1r) antagonist SB-334867, or the orexin 2 receptor (OX2r) antagonist TCS-OX2-29, were then administered directly into the PVT to assess the effects of these pharmacological agents on the expression of PavCA behavior and on the conditioned reinforcing properties of the Pavlovian reward cue.ResultsLesions of the LHA before training attenuated the development of lever-directed (sign-tracking) behaviors in the PavCA paradigm, without affecting magazine-directed (goal-tracking) behaviors. In STs, administration of the OX1r antagonist into the PVT reduced lever-directed behaviors and increased magazine-directed behaviors; while administration of the OX2r antagonist only reduced lever-directed behaviors. Further, OX2r, but not OX1r, antagonism was able to reduce the incentive motivational value of the conditioned stimulus on a conditioned reinforcement test in STs. The behavior of GTs was unaffected by orexinergic antagonism in the PVT.ConclusionsThe LHA is necessary for the attribution of incentive salience to reward cues and, thereby, the development of a sign-tracking conditioned response. Furthermore, blockade of orexin signaling in the PVT attenuates the incentive value of a Pavlovian reward cue. These data suggest that hypothalamic orexin inputs to the PVT are a key component of the circuitry that encodes the incentive motivational value of reward cues and promotes maladaptive cue-driven behaviors.


2012 ◽  
Vol 226 (2) ◽  
pp. 571-578 ◽  
Author(s):  
Arthur Tomie ◽  
Michelle Lincks ◽  
Steffi D. Nadarajah ◽  
Larissa A. Pohorecky ◽  
Lei Yu

2019 ◽  
Author(s):  
Yanaira Alonso-Caraballo ◽  
Carrie R. Ferrario

AbstractNaturally occurring alterations in estradiol influence food intake in females. However, how motivational responses to food cues are affected by the estrous cycle or ovarian hormones is unknown. In addition, while individual susceptibility to obesity is accompanied by enhanced incentive motivational responses to food cues and increased NAc intrinsic excitability in males, studies in females are absent. Here, we examined basal differences in intrinsic NAc excitability of obesity-prone vs. obesity-resistant females and determined how conditioned approach (a measure of cue-triggered motivation), food intake, and motivation for food vary with the cycle in naturally cycling female obesity-prone, obesity-resistant, and outbred Sprague-Dawley rats. Finally, we used ovariectomy followed by hormone treatment to determine the role of ovarian hormones in cue-triggered motivation in selectively-bred and outbred female rats. We found that intrinsic excitability of NAc MSNs and conditioned approach are enhanced in female obesity-prone vs. obesity-resistant rats. These effects were driven by greater MSN excitability and conditioned approach behavior during metestrus/diestrus vs. proestrus/estrus in obesity-prone but not obesity-resistant rats, despite similar regulation of food intake and food motivation by the cycle in these groups. Furthermore, estradiol and progesterone treatment reduced conditioned approach behavior in obesity-prone and outbred Sprague-Dawley females. To our knowledge, these data are the first to demonstrate cycle- and hormone-dependent effects on the motivational response to a food cue, and the only studies to date to determine how individual susceptibility to obesity influences NAc excitability, cue-triggered food-seeking, and differences in the regulation of these neurobehavioral responses by the cycle.


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