Pharmacological effects of cannabinoids on the reference and working memory functions in mice

Avdesh, Avdesh; Hoe, Yikai; Martins, Ralph N.; Martin‐Iverson, Mathew T.

doi:10.1007/s00213-012-2834-6

Cited by 15 publications

(5 citation statements)

References 61 publications

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“…Of note, CCK-GABA cells are the only type of cortical interneuron that express CB1 receptors (Marsicano and Lutz, 1999;Takács et al, 2015). Consistent with our finding, impaired working memory is a well-established consequence of CB1 receptor binding by exogenous cannabinoids applied systemically and locally in the mPFC (Varvel et al, 2001;Varvel and Lichtman, 2002;De Melo et al, 2005;Avdesh et al, 2013). Adolescent cannabinoid use has been implicated in the increased risk of developing schizophrenia (Moore et al, 2007), a condition in which working memory impairments are a core deficit (Forbes et al, 2009;Gold et al, 2010;Anticevic et al, 2011).…”

Section: Discussionsupporting

confidence: 87%

Cholecystokinin-Expressing Interneurons of the Medial Prefrontal Cortex Mediate Working Memory Retrieval

et al. 2020

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Distinct components of working memory are coordinated by different classes of inhibitory interneurons in the PFC, but the role of cholecystokinin (CCK)-positive interneurons remains enigmatic. In humans, this major population of interneurons shows histological abnormalities in schizophrenia, an illness in which deficient working memory is a core defining symptom and the best predictor of long-term functional outcome. Yet, CCK interneurons as a molecularly distinct class have proved intractable to examination by typical molecular methods due to widespread expression of CCK in the pyramidal neuron population. Using an intersectional approach in mice of both sexes, we have succeeded in labeling, interrogating, and manipulating CCK interneurons in the mPFC. Here, we describe the anatomical distribution, electrophysiological properties, and postsynaptic connectivity of CCK interneurons, and evaluate their role in cognition. We found that CCK interneurons comprise a larger proportion of the mPFC interneurons compared with parvalbumin interneurons, targeting a wide range of neuronal subtypes with a distinct connectivity pattern. Phase-specific optogenetic inhibition revealed that CCK, but not parvalbumin, interneurons play a critical role in the retrieval of working memory. These findings shine new light on the relationship between cortical CCK interneurons and cognition and offer a new set of tools to investigate interneuron dysfunction and cognitive impairments associated with schizophrenia.

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Section: Discussionsupporting

confidence: 87%

Cholecystokinin-Expressing Interneurons of the Medial Prefrontal Cortex Mediate Working Memory Retrieval

et al. 2020

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“…Systemic administration of CP 55,940, WIN 55,212-2, and ACEA affected working memory [ 95 ] and object recognition memory in rats [ 96 , 97 ]. A similar effect using CP 55,940 was also reported in mice [ 98 ]. The negative effects of synthetic cannabinoids (WIN 55,212-2 and CP 55,940) on learning and memory appear to be directly linked to the inhibition of acetylcholine release in the hippocampal region [ 99 , 100 ] and the inhibition of glutamatergic synaptic transmission in the prefrontal cortex [ 101 , 102 ].…”

Section: Cannabinoids and Endocannabinoid Systemssupporting

confidence: 78%

Potential and Limits of Cannabinoids in Alzheimer’s Disease Therapy

Abate

Uberti

Tambaro

2021

Biology

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Alzheimer’s disease (AD) is a detrimental brain disorder characterized by a gradual cognitive decline and neuronal deterioration. To date, the treatments available are effective only in the early stage of the disease. The AD etiology has not been completely revealed, and investigating new pathological mechanisms is essential for developing effective and safe drugs. The recreational and pharmacological properties of marijuana are known for centuries, but only recently the scientific community started to investigate the potential use of cannabinoids in AD therapy—sometimes with contradictory outcomes. Since the endocannabinoid system (ECS) is highly expressed in the hippocampus and cortex, cannabis use/abuse has often been associated with memory and learning dysfunction in vulnerable individuals. However, the latest findings in AD rodent models have shown promising effects of cannabinoids in reducing amyloid plaque deposition and stimulating hippocampal neurogenesis. Beneficial effects on several dementia-related symptoms have also been reported in clinical trials after cannabinoid treatments. Accordingly, future studies should address identifying the correct therapeutic dosage and timing of treatment from the perspective of using cannabinoids in AD therapy. The present paper aims to summarize the potential and limitations of cannabinoids as therapeutics for AD, focusing on recent pre-clinical and clinical evidence.

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“…For the SR141716A (SR) experiments, SR (gift from RBI, Natick, MA) was dissolved in 10μl of ethanol followed by a few drops of Tween 80 and then volume was made up with sterile saline solution. The SR solution was administered (3 mg/kg) by IP injection at a volume of 10ml/kg body weight 30 min (Lichtman and Martin, ; Varvel et al, ; Avdesh et al, ) before JWH‐081 administration. The SR vehicle solution was injected as a control.…”

Section: Methodsmentioning

confidence: 99%

CB1 receptor-mediated signaling underlies the hippocampal synaptic, learning, and memory deficits following treatment with JWH-081, a new component of spice/K2 preparations

Basavarajappa

Subbanna

2013

Hippocampus

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Recently, synthetic cannabinoids have been sprayed onto plant material, which is subsequently packaged and sold as “Spice” or “K2” to mimic the effects of marijuana. A recent report identified several synthetic additives in samples of “Spice/K2”, including JWH-081, a synthetic ligand for the cannabinoid receptor 1 (CB1). The deleterious effects of JWH-081 on brain function are not known, particularly on CB1 signaling, synaptic plasticity, learning and memory. Here, we evaluated the effects of JWH-081 on pCaMKIV, pCREB and pERK1/2 signaling events followed by long-term potentiation (LTP), hippocampal-dependent learning and memory tasks using CB1 receptor wild type (WT) and knockout (KO) mice. Acute administration of JWH-081 impaired CaMKIV phosphorylation in a dose-dependent manner, whereas inhibition of CREB phosphorylation in CB1 receptor WT mice was observed only at higher dose of JWH-081 (1.25 mg/kg). JWH-081 at higher dose impaired CaMKIV and CREB phosphorylation in a time –dependent manner in CB1 receptor WT mice but not in KO mice and failed to alter ERK1/2 phosphorylation. In addition, SR treated or CB1 receptor KO mice have a lower pCaMKIV/CaMKIV ratio and higher pCREB/CREB ratio compared to vehicle or WT littermates. In hippocampal slices, JWH-081 impaired LTP in CB1 receptor WT but not in KO littermates. Furthermore, JWH-081 at higher dose impaired object recognition, spontaneous alternation and spatial memory on the Y-maze in CB1 receptor WT mice but not in KO mice. Collectively our findings suggest that deleterious effects of JWH-081 on hippocampal function involves CB1 receptor mediated impairments in CaMKIV and CREB phosphorylation, LTP, learning and memory in mice.

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Pharmacological effects of cannabinoids on the reference and working memory functions in mice

Abstract: The present study provides evidence for a strain-specific effect of a dose of CP 55940 on reference memory. While the cannabinoid agonist also impaired working memory in one strain, this effect was apparently not mediated by CB1 receptors.

Cited by 15 publications

References 61 publications

Cholecystokinin-Expressing Interneurons of the Medial Prefrontal Cortex Mediate Working Memory Retrieval

Cholecystokinin-Expressing Interneurons of the Medial Prefrontal Cortex Mediate Working Memory Retrieval

Potential and Limits of Cannabinoids in Alzheimer’s Disease Therapy

CB1 receptor-mediated signaling underlies the hippocampal synaptic, learning, and memory deficits following treatment with JWH-081, a new component of spice/K2 preparations

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