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Decreased reward sensitivity in rats from the Fischer344 strain compared to Wistar rats is paralleled by differences in endocannabinoid signaling.

Brand T, Spanagel R, Schneider M - PLoS ONE (2012)

Bottom Line: These differences were observed for consummatory, motivational and hedonic aspects of the palatable food reward.These findings were further supported by the pharmacological results, where Fischer rats were found to be less sensitive towards the effects of the CB1 receptor antagonist/inverse agonist SR141716 and the cannabinoid agonist WIN 55,212-2.These basic differences in the ECB system might contribute to the pronounced differences observed in reward sensitivity between both rat strains.

View Article: PubMed Central - PubMed

Affiliation: Research Group Developmental Neuropsychopharmacology, Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

ABSTRACT

Background: The aim of the present study was to examine if differences in the endocannabinoid (ECB) system might be linked to strain specific variations in reward-related behavior in Fischer344 (Fischer) and Wistar rats.

Methodology/principal findings: Two rat strains, the Fischer and the Wistar strain, were tested for different aspects of reward sensitivity for a palatable food reward (sweetened condensed milk, SCM) in a limited-access intake test, a progressive ratio (PR) schedule and the pleasure-attenuated startle (PAS) paradigm. Additionally, basic differences in the ECB system and cannabinoid pharmacology were examined in both rat strains. Fischer rats were found to express lower reward sensitivity towards SCM compared to Wistar rats. These differences were observed for consummatory, motivational and hedonic aspects of the palatable food reward. Western blot analysis for the CB1 receptor and the ECB degrading enzyme fatty acid amide hydrolase (FAAH) revealed a lower expression of both proteins in the hippocampus (HPC) of Fischer rats compared to the Wistar strain. Furthermore, increased cannabinoid-stimulated extracellular-regulated kinase (ERK) phosphorylation was detected in Wistar rats compared to the Fischer strain, indicating alterations in ECB signaling. These findings were further supported by the pharmacological results, where Fischer rats were found to be less sensitive towards the effects of the CB1 receptor antagonist/inverse agonist SR141716 and the cannabinoid agonist WIN 55,212-2.

Conclusions/significance: Our present findings indicate differences in the expression of the CB1 receptor and FAAH, as well as the activation of ECB signaling pathways between Fischer and Wistar rats. These basic differences in the ECB system might contribute to the pronounced differences observed in reward sensitivity between both rat strains.

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Strain specific effects of SR141716 (SR) on SCM intake.SCM intake in Wistar (A) and Fischer rats (B), as well as percentage reduction of SCM consumption (B) in both strains (C). All three concentrations of SR significantly reduced SCM intake in Wistar rats (A) (p<0.05 is indicated by one asterisk; p<0.001 is indicated by two asterisks). In addition, SCM intake in Wistar rats after treatment with 1.2 mg/kg SR was also significantly reduced compared to treatment with the lowest dose (p<0.05 is indicated by one diamond). In Fischer rats only the two highest concentrations of SR induced a significant attenuation of SCM intake compared to vehicle treatment (B) (p<0.05 is indicated by one asterisk). The percentage inhibition of SCM intake (C) induced by SR was overall significantly stronger in the Wistar strain compared to Fischer rats. Values are expressed as means ± SEM.
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pone-0031169-g005: Strain specific effects of SR141716 (SR) on SCM intake.SCM intake in Wistar (A) and Fischer rats (B), as well as percentage reduction of SCM consumption (B) in both strains (C). All three concentrations of SR significantly reduced SCM intake in Wistar rats (A) (p<0.05 is indicated by one asterisk; p<0.001 is indicated by two asterisks). In addition, SCM intake in Wistar rats after treatment with 1.2 mg/kg SR was also significantly reduced compared to treatment with the lowest dose (p<0.05 is indicated by one diamond). In Fischer rats only the two highest concentrations of SR induced a significant attenuation of SCM intake compared to vehicle treatment (B) (p<0.05 is indicated by one asterisk). The percentage inhibition of SCM intake (C) induced by SR was overall significantly stronger in the Wistar strain compared to Fischer rats. Values are expressed as means ± SEM.

Mentions: Treatment with the CB1 receptor antagonist/inverse agonist SR reduced SCM intake dose-dependently in both Wistar (F3,27 = 11.2, p<0.05) and Fischer rats (F3,30 = 5.3, p<0.05) (Figure 5). Post-hoc analysis revealed that all three doses of SR decreased SCM intake in Wistar rats compared to vehicle treatment (SR 0.3: p = 0.044, SR 0.6: p = 0.002, SR 1.2: p<0.001). Furthermore, the highest dose SR differed also significantly from the 0.3 mg/kg concentration (p = 0.005) (Figure 5 A).


Decreased reward sensitivity in rats from the Fischer344 strain compared to Wistar rats is paralleled by differences in endocannabinoid signaling.

Brand T, Spanagel R, Schneider M - PLoS ONE (2012)

Strain specific effects of SR141716 (SR) on SCM intake.SCM intake in Wistar (A) and Fischer rats (B), as well as percentage reduction of SCM consumption (B) in both strains (C). All three concentrations of SR significantly reduced SCM intake in Wistar rats (A) (p<0.05 is indicated by one asterisk; p<0.001 is indicated by two asterisks). In addition, SCM intake in Wistar rats after treatment with 1.2 mg/kg SR was also significantly reduced compared to treatment with the lowest dose (p<0.05 is indicated by one diamond). In Fischer rats only the two highest concentrations of SR induced a significant attenuation of SCM intake compared to vehicle treatment (B) (p<0.05 is indicated by one asterisk). The percentage inhibition of SCM intake (C) induced by SR was overall significantly stronger in the Wistar strain compared to Fischer rats. Values are expressed as means ± SEM.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3275578&req=5

pone-0031169-g005: Strain specific effects of SR141716 (SR) on SCM intake.SCM intake in Wistar (A) and Fischer rats (B), as well as percentage reduction of SCM consumption (B) in both strains (C). All three concentrations of SR significantly reduced SCM intake in Wistar rats (A) (p<0.05 is indicated by one asterisk; p<0.001 is indicated by two asterisks). In addition, SCM intake in Wistar rats after treatment with 1.2 mg/kg SR was also significantly reduced compared to treatment with the lowest dose (p<0.05 is indicated by one diamond). In Fischer rats only the two highest concentrations of SR induced a significant attenuation of SCM intake compared to vehicle treatment (B) (p<0.05 is indicated by one asterisk). The percentage inhibition of SCM intake (C) induced by SR was overall significantly stronger in the Wistar strain compared to Fischer rats. Values are expressed as means ± SEM.
Mentions: Treatment with the CB1 receptor antagonist/inverse agonist SR reduced SCM intake dose-dependently in both Wistar (F3,27 = 11.2, p<0.05) and Fischer rats (F3,30 = 5.3, p<0.05) (Figure 5). Post-hoc analysis revealed that all three doses of SR decreased SCM intake in Wistar rats compared to vehicle treatment (SR 0.3: p = 0.044, SR 0.6: p = 0.002, SR 1.2: p<0.001). Furthermore, the highest dose SR differed also significantly from the 0.3 mg/kg concentration (p = 0.005) (Figure 5 A).

Bottom Line: These differences were observed for consummatory, motivational and hedonic aspects of the palatable food reward.These findings were further supported by the pharmacological results, where Fischer rats were found to be less sensitive towards the effects of the CB1 receptor antagonist/inverse agonist SR141716 and the cannabinoid agonist WIN 55,212-2.These basic differences in the ECB system might contribute to the pronounced differences observed in reward sensitivity between both rat strains.

View Article: PubMed Central - PubMed

Affiliation: Research Group Developmental Neuropsychopharmacology, Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

ABSTRACT

Background: The aim of the present study was to examine if differences in the endocannabinoid (ECB) system might be linked to strain specific variations in reward-related behavior in Fischer344 (Fischer) and Wistar rats.

Methodology/principal findings: Two rat strains, the Fischer and the Wistar strain, were tested for different aspects of reward sensitivity for a palatable food reward (sweetened condensed milk, SCM) in a limited-access intake test, a progressive ratio (PR) schedule and the pleasure-attenuated startle (PAS) paradigm. Additionally, basic differences in the ECB system and cannabinoid pharmacology were examined in both rat strains. Fischer rats were found to express lower reward sensitivity towards SCM compared to Wistar rats. These differences were observed for consummatory, motivational and hedonic aspects of the palatable food reward. Western blot analysis for the CB1 receptor and the ECB degrading enzyme fatty acid amide hydrolase (FAAH) revealed a lower expression of both proteins in the hippocampus (HPC) of Fischer rats compared to the Wistar strain. Furthermore, increased cannabinoid-stimulated extracellular-regulated kinase (ERK) phosphorylation was detected in Wistar rats compared to the Fischer strain, indicating alterations in ECB signaling. These findings were further supported by the pharmacological results, where Fischer rats were found to be less sensitive towards the effects of the CB1 receptor antagonist/inverse agonist SR141716 and the cannabinoid agonist WIN 55,212-2.

Conclusions/significance: Our present findings indicate differences in the expression of the CB1 receptor and FAAH, as well as the activation of ECB signaling pathways between Fischer and Wistar rats. These basic differences in the ECB system might contribute to the pronounced differences observed in reward sensitivity between both rat strains.

Show MeSH
Related in: MedlinePlus