Evaluation of CB1 receptor knockout mice in the Morris water maze

被引:188
作者
Varvel, SA [1 ]
Lichtman, AH [1 ]
机构
[1] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA
关键词
D O I
10.1124/jpet.301.3.915
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The endocannabinoid system has been proposed to modulate a variety of physiological processes, including those that underlie cognition. The present study tested whether this system is tonically active in learning and memory by comparing CB1 receptor knockout mice (CB1-/-) to wild-type mice (CB1+/+) in several Morris water maze tasks. Also, the effects of three cannabinoid agonists, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), R-(+)-[2,3-dihydro-5-methyl-3[morpholinyl) methyl]- pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate (WIN 55,212-2), and methanandamide, were evaluated in a working memory procedure. Both genotypes exhibited identical acquisition rates in a fixed platform procedure; however, the CB1-/- mice demonstrated significant deficits in a reversal task in which the location of the hidden platform was moved to the opposite side of the tank. This phenotype difference was most likely due to an increased perseverance of the CB1-/- mice in that they continued to return to the original platform location, despite being repeatedly shown the new platform location. In addition, Delta9-THC (ED50=1.3 mg/kg), WIN 55,212-2 (ED50=0.35 mg/kg), and methanandamide (ED50=3.2 mg/kg) disrupted the performance of CB1+/+ mice in the working memory task at doses that did not elicit motivational or sensorimotor impairment as assessed in a cued version of the task. Furthermore, doses of each drug that were maximally disruptive in CB1+/+ mice were ineffective in either N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4methyl-1H-pyrazole-3-carboxamide HCl (SR 141716A) treated CB1+/+ or CB1-/- mice. These results provide strong evidence that cannabinoids disrupt working memory through a CB1 receptor mechanism of action, and suggest that the endocannabinoid system may have a role in facilitating extinction and/or forgetting processes.
引用
收藏
页码:915 / 924
页数:10
相关论文
共 50 条
[31]   Age-related changes of anandamide metabolism in CB1 cannabinoid receptor knockout mice:: correlation with behaviour [J].
Maccarrone, M ;
Valverde, O ;
Barbaccia, ML ;
Castañé, A ;
Maldonado, R ;
Ledent, C ;
Parmentier, M ;
Finazzi-Agrò, A .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2002, 15 (07) :1178-1186
[32]   Lack of morphine-induced dopamine release in the nucleus accumbens of cannabinoid CB1 receptor knockout mice [J].
Mascia, MS ;
Obinu, MC ;
Ledent, C ;
Parmentier, M ;
Böhme, GA ;
Imperato, A ;
Fratta, W .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1999, 383 (03) :R1-R2
[33]   Impaired water maze learning performance in μ-opioid receptor knockout mice [J].
Jang, CG ;
Lee, SY ;
Yoo, JH ;
Yan, JJ ;
Song, DK ;
Loh, HH ;
Ho, IK .
MOLECULAR BRAIN RESEARCH, 2003, 117 (01) :68-72
[34]   Hypothermia in mice tested in Morris water maze [J].
Iivonen, H ;
Nurminen, L ;
Harri, M ;
Tanila, H ;
Puoliväli, J .
BEHAVIOURAL BRAIN RESEARCH, 2003, 141 (02) :207-213
[35]   NEURONAL CONTROL OF MICTURITION VIA CANNABINOID (CB) TYPE 1 RECEPTORS - EVALUATION OF A CB1 KNOCKOUT MOUSE [J].
Fuellhase, Claudius ;
Campeau, Lysanne ;
Sibaev, Andrei ;
Storr, Martin ;
Gratzke, Christian ;
Stief, Christian ;
Hedlund, Petter ;
Andersson, Karl-Erik .
JOURNAL OF UROLOGY, 2013, 189 (04) :E48-E49
[36]   Increased brain expression of CREB and neuropeptide Y are associated with reduced alcohol intake in CB1 receptor knockout mice [J].
Prakash, A. ;
Vinod, K. Y. ;
Roy, A. ;
Yalamanchili, R. K. ;
Hungund, B. L. ;
Pandey, S. C. .
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 2008, 32 (06) :146A-146A
[37]   CB1 receptor knockout mice show similar behavioral modifications to wild-type mice when enkephalin catabolism is inhibited [J].
Jardinaud, F ;
Crété, D ;
Canestrelli, C ;
Ledent, C ;
Roques, BP ;
Noble, F .
BRAIN RESEARCH, 2005, 1063 (01) :77-83
[38]   BDNF impairment in the hippocampus is related to enhanced despair behavior in CB1 knockout mice [J].
Aso, Ester ;
Ozaita, Andres ;
Valdizan, Elsa M. ;
Ledent, Catherine ;
Pazos, Angel ;
Maldonado, Rafael ;
Valverde, Olga .
JOURNAL OF NEUROCHEMISTRY, 2008, 105 (02) :565-572
[39]   Methylphenidate, but not antipsychotics, improves prepulse inhibition deficits displayed by CB1 knockout mice [J].
Navarrete Rueda, F. ;
Ortega-Alvaro, A. ;
Aracil-Fernandez, A. ;
Ternianov, A. ;
Manzanares, J. .
EUROPEAN NEUROPSYCHOPHARMACOLOGY, 2013, 23 :S210-S210
[40]   The effects of cannabinoids on contextual, conditioned fear in CB1 knockout and CD1 mice [J].
Mikics, Eva ;
Dombi, Timea ;
Barsvari, Beata ;
Varga, Balazs ;
Ledent, Catherine ;
Freund, Tamas F. ;
Haller, Jozsef .
BEHAVIOURAL PHARMACOLOGY, 2006, 17 (03) :223-230