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Dysfunction in fatty acid amide hydrolase is associated with depressive-like behavior in Wistar Kyoto rats.

Vinod KY, Xie S, Psychoyos D, Hungund BL, Cooper TB, Tejani-Butt SM - PLoS ONE (2012)

Bottom Line: Immunoblot analysis indicated significantly higher levels of fatty acid amide hydrolase (FAAH) in frontal cortex and hippocampus of WKY rats with no alteration in the level of N-arachidonyl phosphatidyl ethanolamine specific phospholipase-D (NAPE-PLD).Significantly higher levels of CB1 receptor-mediated G-protein coupling and lower levels of anandamide (AEA) were found in frontal cortex and hippocampus of WKY rats.While the levels of brain derived neurotropic factor (BDNF) were significantly lower in frontal cortex and hippocampus of WKY rats compared to WIS rats, pharmacological inhibition of FAAH elevated BDNF levels in WKY rats.

View Article: PubMed Central - PubMed

Affiliation: Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, United States of America. vyaragudri@nki.rfmh.org

ABSTRACT

Background: While the etiology of depression is not clearly understood at the present time, this mental disorder is thought be a complex and multifactorial trait with important genetic and environmental contributing factors.

Methodology/principal findings: The role of the endocannabinoid (eCB) system in depressive behavior was examined in Wistar Kyoto (WKY) rat strain, a genetic model of depression. Our findings revealed selective abnormalities in the eCB system in the brains of WKY rats compared to Wistar (WIS) rats. Immunoblot analysis indicated significantly higher levels of fatty acid amide hydrolase (FAAH) in frontal cortex and hippocampus of WKY rats with no alteration in the level of N-arachidonyl phosphatidyl ethanolamine specific phospholipase-D (NAPE-PLD). Significantly higher levels of CB1 receptor-mediated G-protein coupling and lower levels of anandamide (AEA) were found in frontal cortex and hippocampus of WKY rats. While the levels of brain derived neurotropic factor (BDNF) were significantly lower in frontal cortex and hippocampus of WKY rats compared to WIS rats, pharmacological inhibition of FAAH elevated BDNF levels in WKY rats. Inhibition of FAAH enzyme also significantly increased sucrose consumption and decreased immobility in the forced swim test in WKY rats.

Conclusions/significance: These findings suggest a critical role for the eCB system and BDNF in the genetic predisposition to depressive-like behavior in WKY rats and point to the potential therapeutic utility of eCB enhancing agents in depressive disorder.

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Related in: MedlinePlus

Effect of FAAH inhibition on BDNF, AEA and CB1 function in the brain of WKY rats.Basal BDNF levels were found to be significantly lower in frontal cortex (27%) and hippocampus (26%) of WKY compared to WIS rats (p<0.05; A). Subchronic treatment with URB597 (0.3 mg/kg, i.p. for 7 days) significantly elevated BDNF levels in frontal cortex (64%) and hippocampus (45%) of WKY rats compared to vehicle treated WKY rats (p<0.05; B). Inhibition of FAAH was accompanied by significant increase in AEA levels in frontal cortex (31%, p<0.01; C) and hippocampus (42%, p<0.001; C), and a subsequent decrease in CB1 receptor-mediated G-protein activation in frontal cortex of WKY rats (21%, p<0.05; D). Hippo; Hippocampus.
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pone-0036743-g005: Effect of FAAH inhibition on BDNF, AEA and CB1 function in the brain of WKY rats.Basal BDNF levels were found to be significantly lower in frontal cortex (27%) and hippocampus (26%) of WKY compared to WIS rats (p<0.05; A). Subchronic treatment with URB597 (0.3 mg/kg, i.p. for 7 days) significantly elevated BDNF levels in frontal cortex (64%) and hippocampus (45%) of WKY rats compared to vehicle treated WKY rats (p<0.05; B). Inhibition of FAAH was accompanied by significant increase in AEA levels in frontal cortex (31%, p<0.01; C) and hippocampus (42%, p<0.001; C), and a subsequent decrease in CB1 receptor-mediated G-protein activation in frontal cortex of WKY rats (21%, p<0.05; D). Hippo; Hippocampus.

Mentions: Basal levels of BDNF were found to be significantly lower in frontal cortex (27%) and hippocampus (26%) of WKY rats compared to WIS rats (p<0.05; n = 4−6; Fig. 5A). Subchronic URB597 treatment (0.3 mg/kg, i.p. for 7 days) markedly elevated BDNF levels in frontal cortex (64%) and hippocampus (45%) of WKY rats compared to vehicle treated WKY rats (p<0.05; n = 4−6; Fig. 5B). This treatment was accompanied by significant increase in AEA levels in frontal cortex (31%, p<0.01; Fig. 5C) and hippocampus (42%, p<0.001; Fig. 5C), and decrease in CB1 receptor-mediated G-protein activation (21%, p<0.05; Fig. 5D) in frontal cortex of WKY rats compared to vehicle treated WKY rats (n = 4−6).


Dysfunction in fatty acid amide hydrolase is associated with depressive-like behavior in Wistar Kyoto rats.

Vinod KY, Xie S, Psychoyos D, Hungund BL, Cooper TB, Tejani-Butt SM - PLoS ONE (2012)

Effect of FAAH inhibition on BDNF, AEA and CB1 function in the brain of WKY rats.Basal BDNF levels were found to be significantly lower in frontal cortex (27%) and hippocampus (26%) of WKY compared to WIS rats (p<0.05; A). Subchronic treatment with URB597 (0.3 mg/kg, i.p. for 7 days) significantly elevated BDNF levels in frontal cortex (64%) and hippocampus (45%) of WKY rats compared to vehicle treated WKY rats (p<0.05; B). Inhibition of FAAH was accompanied by significant increase in AEA levels in frontal cortex (31%, p<0.01; C) and hippocampus (42%, p<0.001; C), and a subsequent decrease in CB1 receptor-mediated G-protein activation in frontal cortex of WKY rats (21%, p<0.05; D). Hippo; Hippocampus.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3351478&req=5

pone-0036743-g005: Effect of FAAH inhibition on BDNF, AEA and CB1 function in the brain of WKY rats.Basal BDNF levels were found to be significantly lower in frontal cortex (27%) and hippocampus (26%) of WKY compared to WIS rats (p<0.05; A). Subchronic treatment with URB597 (0.3 mg/kg, i.p. for 7 days) significantly elevated BDNF levels in frontal cortex (64%) and hippocampus (45%) of WKY rats compared to vehicle treated WKY rats (p<0.05; B). Inhibition of FAAH was accompanied by significant increase in AEA levels in frontal cortex (31%, p<0.01; C) and hippocampus (42%, p<0.001; C), and a subsequent decrease in CB1 receptor-mediated G-protein activation in frontal cortex of WKY rats (21%, p<0.05; D). Hippo; Hippocampus.
Mentions: Basal levels of BDNF were found to be significantly lower in frontal cortex (27%) and hippocampus (26%) of WKY rats compared to WIS rats (p<0.05; n = 4−6; Fig. 5A). Subchronic URB597 treatment (0.3 mg/kg, i.p. for 7 days) markedly elevated BDNF levels in frontal cortex (64%) and hippocampus (45%) of WKY rats compared to vehicle treated WKY rats (p<0.05; n = 4−6; Fig. 5B). This treatment was accompanied by significant increase in AEA levels in frontal cortex (31%, p<0.01; Fig. 5C) and hippocampus (42%, p<0.001; Fig. 5C), and decrease in CB1 receptor-mediated G-protein activation (21%, p<0.05; Fig. 5D) in frontal cortex of WKY rats compared to vehicle treated WKY rats (n = 4−6).

Bottom Line: Immunoblot analysis indicated significantly higher levels of fatty acid amide hydrolase (FAAH) in frontal cortex and hippocampus of WKY rats with no alteration in the level of N-arachidonyl phosphatidyl ethanolamine specific phospholipase-D (NAPE-PLD).Significantly higher levels of CB1 receptor-mediated G-protein coupling and lower levels of anandamide (AEA) were found in frontal cortex and hippocampus of WKY rats.While the levels of brain derived neurotropic factor (BDNF) were significantly lower in frontal cortex and hippocampus of WKY rats compared to WIS rats, pharmacological inhibition of FAAH elevated BDNF levels in WKY rats.

View Article: PubMed Central - PubMed

Affiliation: Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, United States of America. vyaragudri@nki.rfmh.org

ABSTRACT

Background: While the etiology of depression is not clearly understood at the present time, this mental disorder is thought be a complex and multifactorial trait with important genetic and environmental contributing factors.

Methodology/principal findings: The role of the endocannabinoid (eCB) system in depressive behavior was examined in Wistar Kyoto (WKY) rat strain, a genetic model of depression. Our findings revealed selective abnormalities in the eCB system in the brains of WKY rats compared to Wistar (WIS) rats. Immunoblot analysis indicated significantly higher levels of fatty acid amide hydrolase (FAAH) in frontal cortex and hippocampus of WKY rats with no alteration in the level of N-arachidonyl phosphatidyl ethanolamine specific phospholipase-D (NAPE-PLD). Significantly higher levels of CB1 receptor-mediated G-protein coupling and lower levels of anandamide (AEA) were found in frontal cortex and hippocampus of WKY rats. While the levels of brain derived neurotropic factor (BDNF) were significantly lower in frontal cortex and hippocampus of WKY rats compared to WIS rats, pharmacological inhibition of FAAH elevated BDNF levels in WKY rats. Inhibition of FAAH enzyme also significantly increased sucrose consumption and decreased immobility in the forced swim test in WKY rats.

Conclusions/significance: These findings suggest a critical role for the eCB system and BDNF in the genetic predisposition to depressive-like behavior in WKY rats and point to the potential therapeutic utility of eCB enhancing agents in depressive disorder.

Show MeSH
Related in: MedlinePlus