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Dual fatty acid amide hydrolase and monoacylglycerol lipase blockade produces THC-like Morris water maze deficits in mice.
ACS Chem Neurosci. 2012 May 16; 3(5):369-78.AC

Abstract

Acute administration of Δ(9)-tetrahydrocannabinol (THC) or exposure to marijuana smoke impairs short-term spatial memory in water maze tasks through a CB(1) receptor mechanism of action. N-Arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG) are endogenous cannabinoids that are predominantly metabolized by the respective enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). Although the MAGL inhibitor JZL184 enhances short-term synaptic plasticity, it has yet to be evaluated in the Morris water maze. Previous research demonstrated that simultaneous, complete blockade of FAAH and MAGL produces full blown THC-like effects. Thus, in the following studies we tested whether dual blockade of FAAH and MAGL would impair learning in a repeated acquisition Morris water maze task. Mice treated with the dual FAAH/MAGL inhibitor JZL195 (20 mg/kg) as well as JZL184-treated FAAH -/- mice displayed robust deficits in Morris water maze performance that were similar in magnitude to THC-treated mice. While 20 or 40 mg/kg impaired water maze performance in FAAH -/- mice, only the high dose of JZL184 disrupted performance in FAAH +/+ mice. The memory impairing effects of JZL184 were blocked by the CB(1) receptor antagonist rimonabant. Neither JZL184 nor JZL195 impaired performance in a cued version of the water maze task, arguing against the notion that sensorimotor or motivational deficits accounted for the impaired acquisition performance. JZL184 increased 2-AG levels in the hippocampus, prefrontal cortex, and cerebellum to a similar degree in FAAH -/- and +/+ mice. FAAH -/- mice, regardless of drug treatment, possessed elevated AEA levels in each brain region assessed. The results of this study reveal that concomitant increases in AEA and 2-AG disrupt short-term spatial memory performance in a manner similar to that of THC.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Virginia Commonwealth University, 1217 East Marshall Street, P.O. Box 980613, Richmond, Virginia 23298, United States. lewise@vcu.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22860205

Citation

Wise, Laura E., et al. "Dual Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase Blockade Produces THC-like Morris Water Maze Deficits in Mice." ACS Chemical Neuroscience, vol. 3, no. 5, 2012, pp. 369-78.
Wise LE, Long KA, Abdullah RA, et al. Dual fatty acid amide hydrolase and monoacylglycerol lipase blockade produces THC-like Morris water maze deficits in mice. ACS Chem Neurosci. 2012;3(5):369-78.
Wise, L. E., Long, K. A., Abdullah, R. A., Long, J. Z., Cravatt, B. F., & Lichtman, A. H. (2012). Dual fatty acid amide hydrolase and monoacylglycerol lipase blockade produces THC-like Morris water maze deficits in mice. ACS Chemical Neuroscience, 3(5), 369-78. https://doi.org/10.1021/cn200130s
Wise LE, et al. Dual Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase Blockade Produces THC-like Morris Water Maze Deficits in Mice. ACS Chem Neurosci. 2012 May 16;3(5):369-78. PubMed PMID: 22860205.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dual fatty acid amide hydrolase and monoacylglycerol lipase blockade produces THC-like Morris water maze deficits in mice. AU - Wise,Laura E, AU - Long,Kelly A, AU - Abdullah,Rehab A, AU - Long,Jonathan Z, AU - Cravatt,Benjamin F, AU - Lichtman,Aron H, Y1 - 2012/01/27/ PY - 2011/12/22/received PY - 2012/01/27/accepted PY - 2012/8/4/entrez PY - 2012/8/4/pubmed PY - 2012/8/4/medline KW - 2-arachidonoylglycerol (2-AG) KW - Cannabinoid KW - N-arachidonoylethanolamine (anandamide) KW - fatty acid amide hydrolase (FAAH) KW - memory KW - monoacylglycerol lipase (MAGL) SP - 369 EP - 78 JF - ACS chemical neuroscience JO - ACS Chem Neurosci VL - 3 IS - 5 N2 - Acute administration of Δ(9)-tetrahydrocannabinol (THC) or exposure to marijuana smoke impairs short-term spatial memory in water maze tasks through a CB(1) receptor mechanism of action. N-Arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG) are endogenous cannabinoids that are predominantly metabolized by the respective enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). Although the MAGL inhibitor JZL184 enhances short-term synaptic plasticity, it has yet to be evaluated in the Morris water maze. Previous research demonstrated that simultaneous, complete blockade of FAAH and MAGL produces full blown THC-like effects. Thus, in the following studies we tested whether dual blockade of FAAH and MAGL would impair learning in a repeated acquisition Morris water maze task. Mice treated with the dual FAAH/MAGL inhibitor JZL195 (20 mg/kg) as well as JZL184-treated FAAH -/- mice displayed robust deficits in Morris water maze performance that were similar in magnitude to THC-treated mice. While 20 or 40 mg/kg impaired water maze performance in FAAH -/- mice, only the high dose of JZL184 disrupted performance in FAAH +/+ mice. The memory impairing effects of JZL184 were blocked by the CB(1) receptor antagonist rimonabant. Neither JZL184 nor JZL195 impaired performance in a cued version of the water maze task, arguing against the notion that sensorimotor or motivational deficits accounted for the impaired acquisition performance. JZL184 increased 2-AG levels in the hippocampus, prefrontal cortex, and cerebellum to a similar degree in FAAH -/- and +/+ mice. FAAH -/- mice, regardless of drug treatment, possessed elevated AEA levels in each brain region assessed. The results of this study reveal that concomitant increases in AEA and 2-AG disrupt short-term spatial memory performance in a manner similar to that of THC. SN - 1948-7193 UR - https://www.unboundmedicine.com/medline/citation/22860205/Dual_fatty_acid_amide_hydrolase_and_monoacylglycerol_lipase_blockade_produces_THC_like_Morris_water_maze_deficits_in_mice_ L2 - https://dx.doi.org/10.1021/cn200130s DB - PRIME DP - Unbound Medicine ER -