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Alterations in the endocannabinoid system in the rat valproic acid model of autism.
Behav Brain Res. 2013 Jul 15; 249:124-32.BB

Abstract

The endocannabinoid system plays a crucial role in regulating emotionality and social behaviour, however it is unknown whether this system plays a role in symptoms associated with autism spectrum disorders. The current study evaluated if alterations in the endocannabinoid system accompany behavioural changes in the valproic acid (VPA) rat model of autism. Adolescent rats prenatally exposed to VPA exhibited impaired social investigatory behaviour, hypoalgesia and reduced lococmotor activity on exposure to a novel aversive arena. Levels of the endocananbinoids, anandamide (AEA) and 2-arachidonylglycerol (2-AG) in the hippocampus, frontal cortex or cerebellum were not altered in VPA- versus saline-exposed animals. However, the expression of mRNA for diacylglycerol lipase α, the enzyme primarily responsible for the synthesis of 2-AG, was reduced in the cerebellum of VPA-exposed rats. Furthermore, while the expression of mRNA for the 2-AG-catabolising enzyme monoacylglycerol lipase was reduced, the activity of this enzyme was increased, in the hippocampus of VPA-exposed animals. CB1 or CB2 receptor expression was not altered in any of the regions examined, however VPA-exposed rats exhibited reduced PPARα and GPR55 expression in the frontal cortex and PPARγ and GPR55 expression in the hippocampus, additional receptor targets of the endocannabinoids. Furthermore, tissue levels of the fatty acid amide hydrolase substrates, AEA, oleoylethanolamide and palmitoylethanolamide, were higher in the hippocampus of VPA-exposed rats immediately following social exposure. These data indicate that prenatal VPA exposure is associated with alterations in the brain's endocannabinoid system and support the hypothesis that endocannabinoid dysfunction may underlie behavioural abnormalities observed in autism spectrum disorders.

Authors+Show Affiliations

Physiology, School of Medicine, National University of Ireland Galway, Ireland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23643692

Citation

Kerr, D M., et al. "Alterations in the Endocannabinoid System in the Rat Valproic Acid Model of Autism." Behavioural Brain Research, vol. 249, 2013, pp. 124-32.
Kerr DM, Downey L, Conboy M, et al. Alterations in the endocannabinoid system in the rat valproic acid model of autism. Behav Brain Res. 2013;249:124-32.
Kerr, D. M., Downey, L., Conboy, M., Finn, D. P., & Roche, M. (2013). Alterations in the endocannabinoid system in the rat valproic acid model of autism. Behavioural Brain Research, 249, 124-32. https://doi.org/10.1016/j.bbr.2013.04.043
Kerr DM, et al. Alterations in the Endocannabinoid System in the Rat Valproic Acid Model of Autism. Behav Brain Res. 2013 Jul 15;249:124-32. PubMed PMID: 23643692.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alterations in the endocannabinoid system in the rat valproic acid model of autism. AU - Kerr,D M, AU - Downey,L, AU - Conboy,M, AU - Finn,D P, AU - Roche,M, Y1 - 2013/05/01/ PY - 2013/02/27/received PY - 2013/04/22/revised PY - 2013/04/24/accepted PY - 2013/5/7/entrez PY - 2013/5/7/pubmed PY - 2013/10/22/medline SP - 124 EP - 32 JF - Behavioural brain research JO - Behav. Brain Res. VL - 249 N2 - The endocannabinoid system plays a crucial role in regulating emotionality and social behaviour, however it is unknown whether this system plays a role in symptoms associated with autism spectrum disorders. The current study evaluated if alterations in the endocannabinoid system accompany behavioural changes in the valproic acid (VPA) rat model of autism. Adolescent rats prenatally exposed to VPA exhibited impaired social investigatory behaviour, hypoalgesia and reduced lococmotor activity on exposure to a novel aversive arena. Levels of the endocananbinoids, anandamide (AEA) and 2-arachidonylglycerol (2-AG) in the hippocampus, frontal cortex or cerebellum were not altered in VPA- versus saline-exposed animals. However, the expression of mRNA for diacylglycerol lipase α, the enzyme primarily responsible for the synthesis of 2-AG, was reduced in the cerebellum of VPA-exposed rats. Furthermore, while the expression of mRNA for the 2-AG-catabolising enzyme monoacylglycerol lipase was reduced, the activity of this enzyme was increased, in the hippocampus of VPA-exposed animals. CB1 or CB2 receptor expression was not altered in any of the regions examined, however VPA-exposed rats exhibited reduced PPARα and GPR55 expression in the frontal cortex and PPARγ and GPR55 expression in the hippocampus, additional receptor targets of the endocannabinoids. Furthermore, tissue levels of the fatty acid amide hydrolase substrates, AEA, oleoylethanolamide and palmitoylethanolamide, were higher in the hippocampus of VPA-exposed rats immediately following social exposure. These data indicate that prenatal VPA exposure is associated with alterations in the brain's endocannabinoid system and support the hypothesis that endocannabinoid dysfunction may underlie behavioural abnormalities observed in autism spectrum disorders. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/23643692/Alterations_in_the_endocannabinoid_system_in_the_rat_valproic_acid_model_of_autism_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(13)00251-9 DB - PRIME DP - Unbound Medicine ER -