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Regulation of hippocampal cannabinoid CB1 receptor actions by adenosine A1 receptors and chronic caffeine administration: implications for the effects of Δ9-tetrahydrocannabinol on spatial memory.
Neuropsychopharmacology. 2011 Jan; 36(2):472-87.N

Abstract

The cannabinoid CB(1) receptor-mediated modulation of γ-aminobutyric acid (GABA) release from inhibitory interneurons is important for the integrity of hippocampal-dependent spatial memory. Although adenosine A(1) receptors have a central role in fine-tuning excitatory transmission in the hippocampus, A(1) receptors localized in GABAergic cells do not directly influence GABA release. CB(1) and A(1) receptors are the main targets for the effects of two of the most heavily consumed psychoactive substances worldwide: Δ(9)-tetrahydrocannabinol (THC, a CB(1) receptor agonist) and caffeine (an adenosine receptor antagonist). We first tested the hypothesis that an A(1)-CB(1) interaction influences GABA and glutamate release in the hippocampus. We found that A(1) receptor activation attenuated the CB(1)-mediated inhibition of GABA and glutamate release and this interaction was manifested at the level of G-protein activation. Using in vivo and in vitro approaches, we then investigated the functional implications of the adenosine-cannabinoid interplay that may arise following chronic caffeine consumption. Chronic administration of caffeine in mice (intraperitoneally, 3 mg/kg/day, for 15 days, >12 h before trials) led to an A(1)-mediated enhancement of the CB(1)-dependent acute disruptive effects of THC on a short-term spatial memory task, despite inducing a reduction in cortical and hippocampal CB(1) receptor number and an attenuation of CB(1) coupling with G protein. A(1) receptor levels were increased following chronic caffeine administration. This study shows that A(1) receptors exert a negative modulatory effect on CB(1)-mediated inhibition of GABA and glutamate release, and provides the first evidence of chronic caffeine-induced alterations on the cannabinoid system in the cortex and hippocampus, with functional implications in spatial memory.

Authors+Show Affiliations

Faculty of Medicine, Institute of Pharmacology and Neurosciences, University of Lisbon, Lisbon, Portugal.No affiliation info availableNo 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

20927050

Citation

Sousa, Vasco C., et al. "Regulation of Hippocampal Cannabinoid CB1 Receptor Actions By Adenosine A1 Receptors and Chronic Caffeine Administration: Implications for the Effects of Δ9-tetrahydrocannabinol On Spatial Memory." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 36, no. 2, 2011, pp. 472-87.
Sousa VC, Assaife-Lopes N, Ribeiro JA, et al. Regulation of hippocampal cannabinoid CB1 receptor actions by adenosine A1 receptors and chronic caffeine administration: implications for the effects of Δ9-tetrahydrocannabinol on spatial memory. Neuropsychopharmacology. 2011;36(2):472-87.
Sousa, V. C., Assaife-Lopes, N., Ribeiro, J. A., Pratt, J. A., Brett, R. R., & Sebastião, A. M. (2011). Regulation of hippocampal cannabinoid CB1 receptor actions by adenosine A1 receptors and chronic caffeine administration: implications for the effects of Δ9-tetrahydrocannabinol on spatial memory. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 36(2), 472-87. https://doi.org/10.1038/npp.2010.179
Sousa VC, et al. Regulation of Hippocampal Cannabinoid CB1 Receptor Actions By Adenosine A1 Receptors and Chronic Caffeine Administration: Implications for the Effects of Δ9-tetrahydrocannabinol On Spatial Memory. Neuropsychopharmacology. 2011;36(2):472-87. PubMed PMID: 20927050.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of hippocampal cannabinoid CB1 receptor actions by adenosine A1 receptors and chronic caffeine administration: implications for the effects of Δ9-tetrahydrocannabinol on spatial memory. AU - Sousa,Vasco C, AU - Assaife-Lopes,Natália, AU - Ribeiro,Joaquim A, AU - Pratt,Judith A, AU - Brett,Ros R, AU - Sebastião,Ana M, Y1 - 2010/10/06/ PY - 2010/10/8/entrez PY - 2010/10/12/pubmed PY - 2011/11/15/medline SP - 472 EP - 87 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 36 IS - 2 N2 - The cannabinoid CB(1) receptor-mediated modulation of γ-aminobutyric acid (GABA) release from inhibitory interneurons is important for the integrity of hippocampal-dependent spatial memory. Although adenosine A(1) receptors have a central role in fine-tuning excitatory transmission in the hippocampus, A(1) receptors localized in GABAergic cells do not directly influence GABA release. CB(1) and A(1) receptors are the main targets for the effects of two of the most heavily consumed psychoactive substances worldwide: Δ(9)-tetrahydrocannabinol (THC, a CB(1) receptor agonist) and caffeine (an adenosine receptor antagonist). We first tested the hypothesis that an A(1)-CB(1) interaction influences GABA and glutamate release in the hippocampus. We found that A(1) receptor activation attenuated the CB(1)-mediated inhibition of GABA and glutamate release and this interaction was manifested at the level of G-protein activation. Using in vivo and in vitro approaches, we then investigated the functional implications of the adenosine-cannabinoid interplay that may arise following chronic caffeine consumption. Chronic administration of caffeine in mice (intraperitoneally, 3 mg/kg/day, for 15 days, >12 h before trials) led to an A(1)-mediated enhancement of the CB(1)-dependent acute disruptive effects of THC on a short-term spatial memory task, despite inducing a reduction in cortical and hippocampal CB(1) receptor number and an attenuation of CB(1) coupling with G protein. A(1) receptor levels were increased following chronic caffeine administration. This study shows that A(1) receptors exert a negative modulatory effect on CB(1)-mediated inhibition of GABA and glutamate release, and provides the first evidence of chronic caffeine-induced alterations on the cannabinoid system in the cortex and hippocampus, with functional implications in spatial memory. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/20927050/Regulation_of_hippocampal_cannabinoid_CB1_receptor_actions_by_adenosine_A1_receptors_and_chronic_caffeine_administration:_implications_for_the_effects_of_Δ9_tetrahydrocannabinol_on_spatial_memory_ DB - PRIME DP - Unbound Medicine ER -