Enhancement of memory in cannabinoid CB1 receptor knock-out mice

Reibaud, M.; Obinu, Maria Carmen; Ledent, Catherine; Parmentier, Marc; Böhme, Georg Andrees; Impérato, Assunta

doi:10.1016/s0014-2999(99)00496-3

Cited by 176 publications

(112 citation statements)

References 6 publications

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“…On the other hand, rimonabant facilitated olfactory memory in the social recognition test [11] and working memory in the radial arm maze [12]. In agreement with these pharmacological data, mice lacking CB1R showed an increase in LTP in the hippocampus [60], an improvement in memory retention in the objectrecognition paradigm [11,84] and an increased number of conditional changes in the active avoidance task [85].…”

Section: Mechanisms Underlying Memory Modulation By the Endocannabinosupporting

confidence: 66%

Cellular and intracellular mechanisms involved in the cognitive impairment of cannabinoids

Puighermanal

Busquets-García

Maldonado

et al. 2012

Phil. Trans. R. Soc. B

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Exogenous cannabinoids, such as delta9-tetrahydrocannabinol (THC), as well as the modulation of endogenous cannabinoids, affect cognitive function through the activation of cannabinoid receptors. Indeed, these compounds modulate a number of signalling pathways critically implicated in the deleterious effect of cannabinoids on learning and memory. Thus, the involvement of the mammalian target of rapamycin pathway and extracellular signal-regulated kinases, together with their consequent regulation of cellular processes such as protein translation, play a critical role in the amnesic-like effects of cannabinoids. In this study, we summarize the cellular and molecular mechanisms reported in the modulation of cognitive function by the endocannabinoid system.

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Section: Mechanisms Underlying Memory Modulation By the Endocannabinosupporting

confidence: 66%

Cellular and intracellular mechanisms involved in the cognitive impairment of cannabinoids

Puighermanal

Busquets-García

Maldonado

et al. 2012

Phil. Trans. R. Soc. B

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“…It was previously reported that young Cnr1 −/− animals have a better learning ability in the object (44,45) and partner (26,27) recognition tests, as well as in the operant learning paradigm (26). These paradigms sensitively detect disturbances in the function of many brain areas involved in learning and memory.…”

Section: Discussionmentioning

confidence: 99%

Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging

Albayram

Alferink

Pitsch

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

100

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Brain aging is associated with cognitive decline that is accompanied by progressive neuroinflammatory changes. The endocannabinoid system (ECS) is involved in the regulation of glial activity and influences the progression of age-related learning and memory deficits. Mice lacking the Cnr1 gene (Cnr1 −/− ), which encodes the cannabinoid receptor 1 (CB1), showed an accelerated agedependent deficit in spatial learning accompanied by a loss of principal neurons in the hippocampus. The age-dependent decrease in neuronal numbers in Cnr1 −/− mice was not related to decreased neurogenesis or to epileptic seizures. However, enhanced neuroinflammation characterized by an increased density of astrocytes and activated microglia as well as an enhanced expression of the inflammatory cytokine IL-6 during aging was present in the hippocampus of Cnr1 −/− mice. The ongoing process of pyramidal cell degeneration and neuroinflammation can exacerbate each other and both contribute to the cognitive deficits. Deletion of CB1 receptors from the forebrain GABAergic, but not from the glutamatergic neurons, led to a similar neuronal loss and increased neuroinflammation in the hippocampus as observed in animals lacking CB1 receptors in all cells. Our results suggest that CB1 receptor activity on hippocampal GABAergic neurons protects against age-dependent cognitive decline by reducing pyramidal cell degeneration and neuroinflammation.glial regulation | Morris water maze | stereological quantification | CD40 expression | telemetric EEG recording

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“…CB1 receptors have been involved in learning and memory processes (Reibaud et al, 1999;Martin et al, 2002;Varvel and Lichtman, 2002). However, the impairment to self-administer cocaine in these knockout mice does not seem to be the consequence of a learning and memory alteration.…”

Section: Discussionmentioning

confidence: 99%

Lack of CB1 Cannabinoid Receptor Impairs Cocaine Self-Administration

Sòria

Mendizábal

Touriño

et al. 2005

Neuropsychopharmacol

Self Cite

207

203

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Acute rewarding properties are essential for the establishment of cocaine addiction, and multiple neurochemical processes participate in this complex behavior. In the present study, we used the self-administration paradigm to evaluate the role of CB1 cannabinoid receptors in several aspects of cocaine reward, including acquisition, maintenance, and motivation to seek the drug. For this purpose, both CB1 receptor knockout mice and wild-type littermates were trained to intravenously self-administer cocaine under different schedules. Several cocaine training doses (0.32, 1, and 3.2 mg/kg/infusion) were used in the acquisition studies. Only 25% of CB1 knockout mice vs 75% of their wild-type littermates acquired a reliable operant responding to self-administer the most effective dose of cocaine (1 mg/kg/ infusion), and the number of sessions required to attain this behavior was increased in knockout mice. Animals reaching the acquisition criteria were evaluated for the motivational strength of cocaine as a reinforcer under a progressive ratio schedule. The maximal effort to obtain a cocaine infusion was significantly reduced after the genetic ablation of CB1 receptors. A similar result was obtained after the pharmacological blockade of CB1 receptors with SR141716A in wild-type mice. Moreover, the cocaine dose-response curve was flattened in the knockout group, suggesting that the differences observed between genotypes were related to changes in the reinforcing efficacy of the training dose of cocaine. Self-administration for water and food was not altered in CB1 knockout mice in any of the reinforcement schedules used, which emphasizes the selective impairment of drug reinforcement in these knockout mice. Finally, cocaine effects on mesolimbic dopaminergic transmission were evaluated by in vivo microdialysis in these mice. Acute cocaine administration induced a similar enhancement in the extracellular levels of dopamine in the nucleus accumbens of both CB1 knockout and wild-type mice. This work clearly demonstrates that CB1 receptors play an important role in the consolidation of cocaine reinforcement, although are not required for its acute effects on mesolimbic dopaminergic transmission.

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Enhancement of memory in cannabinoid CB1 receptor knock-out mice

Cited by 176 publications

References 6 publications

Cellular and intracellular mechanisms involved in the cognitive impairment of cannabinoids

Cellular and intracellular mechanisms involved in the cognitive impairment of cannabinoids

Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging

Lack of CB1 Cannabinoid Receptor Impairs Cocaine Self-Administration

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