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

Alcohol ◽  
2014 ◽  
Vol 48 (8) ◽  
pp. 755-763 ◽  
Author(s):  
Alexander James McClory ◽  
Linda Patia Spear
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.


PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e75042 ◽  
Author(s):  
Christopher J. Fitzpatrick ◽  
Shyam Gopalakrishnan ◽  
Elizabeth S. Cogan ◽  
Lindsay M. Yager ◽  
Paul J. Meyer ◽  
...  

2020 ◽  
Vol 10 (11) ◽  
pp. 829
Author(s):  
Meredith E. Gamble ◽  
Marvin R. Diaz

Adolescent alcohol use can lead to numerous consequences, including altered stress reactivity and higher risk for later anxiety and alcohol use disorders. Many studies have examined the consequences of heavy ethanol exposure in adolescence, but far less is understood about lower levels of intoxication. The present study examined moderate adolescent ethanol exposure as a possible factor in increasing stress reactivity in adulthood, measured through general and social anxiety-like behaviors, as well voluntary ethanol intake. Male and female Sprague–Dawley rats underwent an adolescent chronic intermittent ethanol (aCIE) vapor exposure during early adolescence, reaching moderate blood ethanol concentrations. Animals then underwent two days of forced swim stress in adulthood. We found that ethanol-exposed males consumed more ethanol than their air counterparts and an interesting stress and ethanol exposure interaction in males. There were no significant effects on voluntary drinking in females. However, the social interaction test revealed increased play-fighting behavior in ethanol-exposed females and reduced social preference in females after two days of stress exposure. Overall, this work provides evidence for sex-specific, long-term effects of moderate aCIE and susceptibility to acute stress in adulthood.


2020 ◽  
Vol 10 (5) ◽  
pp. 270 ◽  
Author(s):  
Samuel J. Hogarth ◽  
Elvan Djouma ◽  
Maarten van den Buuse

Alcohol use disorder (AUD) is a detrimental disease that develops through chronic ethanol exposure. Reduced brain-derived neurotrophic factor (BDNF) expression has been associated with AUD and alcohol addiction, however the effects of activation of BDNF signalling in the brain on voluntary alcohol intake reinstatement and relapse are unknown. We therefore trained male and female Sprague Dawley rats in operant chambers to self-administer a 10% ethanol solution. Following baseline acquisition and progressive ratio (PR) analysis, rats were split into drug and vehicle groups during alcohol lever extinction. The animals received two weeks of daily IP injection of either the BDNF receptor, TrkB, agonist, 7,8-dihydroxyflavone (7,8-DHF), or vehicle. During acquisition of alcohol self-administration, males had significantly higher absolute numbers of alcohol-paired lever presses and a higher PR breakpoint. However, after adjusting for body weight, the amount of ethanol was not different between the sexes and the PR breakpoint was higher in females than males. Following extinction, alcohol-primed reinstatement in male rats was not altered by pretreatment with 7,8-DHF when adjusted for body weight. In contrast, in female rats, the weight-adjusted potential amount of ethanol, but not absolute numbers of active lever presses, was significantly enhanced by 7,8-DHF treatment during reinstatement. Analysis of spontaneous locomotor activity in automated photocell cages suggested that the effect of 7,8-DHF was not associated with hyperactivity. These results suggest that stimulation of the TrkB receptor may contribute to reward craving and relapse in AUD, particularly in females.


2017 ◽  
Vol 41 (4) ◽  
pp. 846-856 ◽  
Author(s):  
Aric C. Madayag ◽  
Sierra J. Stringfield ◽  
Kathryn J. Reissner ◽  
Charlotte A. Boettiger ◽  
Donita L. Robinson

1998 ◽  
Vol 275 (6) ◽  
pp. G1252-G1258 ◽  
Author(s):  
Chantal A. Rivera ◽  
Blair U. Bradford ◽  
Vitor Seabra ◽  
Ronald G. Thurman

This study investigated the role of endotoxin in the hypermetabolic state or swift increase in alcohol metabolism (SIAM) due to acute ethanol exposure. Female Sprague-Dawley rats (100–120 g) were given ethanol (5 g/kg) by gavage. Endotoxin measured in plasma from portal blood was not detectable in saline-treated controls; however, 90 min after ethanol, endotoxin was increased to 85 ± 14 pg/ml, and endotoxin clearance was diminished by ∼50%. Oxygen uptake in perfused livers was increased 48% by ethanol, and production of PGE2 by isolated Kupffer cells was increased similarly. These effects were blunted by elimination of gram-negative bacteria and endotoxin with antibiotics before ethanol administration. To reproduce ethanol-induced endotoxemia, endotoxin was infused via the mesenteric vein at a rate of 2 ng ⋅ kg−1 ⋅ h−1. Endotoxin mimicked the effect of ethanol on oxygen uptake. The specific Kupffer cell toxicant GdCl3completely prevented increases in oxygen uptake due to endotoxin. These findings demonstrate that endotoxin plays a pivotal role in SIAM, most likely by stimulating eicosanoid release from Kupffer cells.


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.


2020 ◽  
Vol 3 ◽  
Author(s):  
Ryan Kokoska ◽  
Eric Rodriguez ◽  
Bryan Yamamoto

Background and Hypothesis:   Voltage-gated L-type calcium channels (Cav1.2 and Cav1.3) in the hippocampus play important roles in glutamatergic neurotransmission underlying memory and learning. Their overexpression has been implicated in neuroexcitatory cell death and disease states including chronic alcoholism. While increases in Cav1.2 gene expression have been reported in the hippocampus after chronic ethanol exposure in rats, the regional distribution of Cav1.2 protein after voluntary ethanol (EtOH) drinking has not been reported. We hypothesize that the expression of Cav1.2 channels within the hippocampus is increased by EtOH drinking in a region-specific manner.    Methods:  Male Sprague Dawley rats were allowed 28 days of intermittent access to a 10% EtOH solution.  At 24 hours after the last exposure to EtOH, brains were collected and processed for immunohistochemistry. Cav1.2 associated immunofluorescent signal from subregions of the hippocampus was quantified using ImageJ analysis software.     Results:  Immunohistochemical results indicate that Cav1.2 immunoreactivity in the hippocampal stratum granulosum layer within the Dentate Gyrus and the stratum pyramidale layer within CA1 and CA3 regions was increased in response to EtOH treatment. There was no significant change in Cav1.2 immunoreactivity for the CA2 region.     Conclusion:   This study suggests that calcium signaling in subregions of the hippocampus is differentially affected by EtOH consumption that may contribute to eventual calcium-mediated apoptosis.    Impact and Implications:  Understanding the process of EtOH-induced hippocampal calcium signaling presents opportunities for understanding the consequences of chronic alcohol exposure related to hippocampal function including memory and learning, and possible interventional therapies for alcohol damage.  


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