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Hippocampal CB(1) receptors mediate the memory impairing effects of Delta(9)-tetrahydrocannabinol.
Neuropsychopharmacology. 2009 Aug; 34(9):2072-80.N

Abstract

It is firmly established that the hippocampus, a brain region implicated in spatial learning, episodic memory, and consolidation, contains a high concentration of CB(1) receptors. Moreover, systemic and intrahippocampal administration of cannabinoid agonists have been shown to impair hippocampal-dependent memory tasks. However, the degree to which CB(1) receptors in the hippocampus play a specific functional role in the memory disruptive effects of marijuana or its primary psychoactive constituent Delta(9)-tetrahydrocannabinol (Delta(9)-THC) is unknown. This study was designed to determine whether hippocampal CB(1) receptors play a functional role in the memory disruptive effects of systemically administered cannabinoids, using the radial arm maze, a well characterized rodent model of working memory. Male Sprague-Dawley rats were implanted with bilateral cannulae aimed at the CA1 region of the dorsal hippocampus. The CB(1) receptor antagonist, rimonabant, was delivered into the hippocampus before to a systemic injection of either Delta(9)-THC or the potent cannabinoid analog, CP-55,940. Strikingly, intrahippocampal administration of rimonabant completely attenuated the memory disruptive effects of both cannabinoids in the radial arm maze task, but did not affect other pharmacological properties of cannabinoids, as assessed in the tetrad assay (that is, hypomotility, analgesia, catalepsy, and hypothermia). Infusions of rimonabant just dorsal or ventral to the hippocampus did not prevent Delta(9)-THC-induced memory impairment, indicating that its effects on mnemonic function were regionally selective. These findings provide compelling evidence in support of the view that hippocampal CB(1) receptors play a necessary role in the memory disruptive effects of marijuana.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

19322169

Citation

Wise, Laura E., et al. "Hippocampal CB(1) Receptors Mediate the Memory Impairing Effects of Delta(9)-tetrahydrocannabinol." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 34, no. 9, 2009, pp. 2072-80.
Wise LE, Thorpe AJ, Lichtman AH. Hippocampal CB(1) receptors mediate the memory impairing effects of Delta(9)-tetrahydrocannabinol. Neuropsychopharmacology. 2009;34(9):2072-80.
Wise, L. E., Thorpe, A. J., & Lichtman, A. H. (2009). Hippocampal CB(1) receptors mediate the memory impairing effects of Delta(9)-tetrahydrocannabinol. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 34(9), 2072-80. https://doi.org/10.1038/npp.2009.31
Wise LE, Thorpe AJ, Lichtman AH. Hippocampal CB(1) Receptors Mediate the Memory Impairing Effects of Delta(9)-tetrahydrocannabinol. Neuropsychopharmacology. 2009;34(9):2072-80. PubMed PMID: 19322169.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hippocampal CB(1) receptors mediate the memory impairing effects of Delta(9)-tetrahydrocannabinol. AU - Wise,Laura E, AU - Thorpe,Andrew J, AU - Lichtman,Aron H, Y1 - 2009/03/25/ PY - 2009/3/27/entrez PY - 2009/3/27/pubmed PY - 2009/12/16/medline SP - 2072 EP - 80 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 34 IS - 9 N2 - It is firmly established that the hippocampus, a brain region implicated in spatial learning, episodic memory, and consolidation, contains a high concentration of CB(1) receptors. Moreover, systemic and intrahippocampal administration of cannabinoid agonists have been shown to impair hippocampal-dependent memory tasks. However, the degree to which CB(1) receptors in the hippocampus play a specific functional role in the memory disruptive effects of marijuana or its primary psychoactive constituent Delta(9)-tetrahydrocannabinol (Delta(9)-THC) is unknown. This study was designed to determine whether hippocampal CB(1) receptors play a functional role in the memory disruptive effects of systemically administered cannabinoids, using the radial arm maze, a well characterized rodent model of working memory. Male Sprague-Dawley rats were implanted with bilateral cannulae aimed at the CA1 region of the dorsal hippocampus. The CB(1) receptor antagonist, rimonabant, was delivered into the hippocampus before to a systemic injection of either Delta(9)-THC or the potent cannabinoid analog, CP-55,940. Strikingly, intrahippocampal administration of rimonabant completely attenuated the memory disruptive effects of both cannabinoids in the radial arm maze task, but did not affect other pharmacological properties of cannabinoids, as assessed in the tetrad assay (that is, hypomotility, analgesia, catalepsy, and hypothermia). Infusions of rimonabant just dorsal or ventral to the hippocampus did not prevent Delta(9)-THC-induced memory impairment, indicating that its effects on mnemonic function were regionally selective. These findings provide compelling evidence in support of the view that hippocampal CB(1) receptors play a necessary role in the memory disruptive effects of marijuana. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/19322169/Hippocampal_CB_1__receptors_mediate_the_memory_impairing_effects_of_Delta_9__tetrahydrocannabinol_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19322169/ DB - PRIME DP - Unbound Medicine ER -