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The Influence of CB2-Receptor Ligands on the Memory-Related Responses in Connection with Cholinergic Pathways in Mice
Marta Kruk-Slomka1, Agnieszka Dzik1, Grazyna Biala1
1Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 4a Chodzki Str., 20-093 Lublin, Poland.
Abstract:
Background: Dysfunction of the cholinergic system is associated with the development of Alzheimer's disease (AD). One of the new possible strategies for the pharmacological modulation of memory-related problems typical of AD, is connected with the endocannabinoid system (ECS) and the cannabinoid (CB: CB1 and CB2) receptors. Methods: The aim of the study was to determine the influence of the selective CB2 receptor ligands: agonist (JWH 133) and antagonist (AM 630) on different stages of memory and learning in mice, in the context of their interaction with cholinergic pathways. To assess and understand the memory-related effects in mice we used the passive avoidance (PA) test. Results: We revealed that co-administration of non-effective dose of JWH 133 (0.25 mg) or AM 630 (0.25 mg/kg) with the non-effective dose of cholinergic receptor agonist - nicotine (0.05 mg/kg) enhanced cognition in the PA test in mice; however, an acute injection of JWH 133 (0.25 mg/kg) or AM 630 (0.25 mg/kg) had no influence on memory enhancement induced by the effective dose of nicotine (0.1 mg/kg). Co-administration of JWH 133 (0.25 mg) or AM 630 (0.25 mg/kg) with the effective dose of the cholinergic receptor antagonist scopolamine (1 mg/kg) attenuated the scopolamine-induced memory impairment in the PA test in mice. Conclusion: Our experiments have shown that CB2 receptors participate in the modulation of memory-related responses, especially those in which cholinergic pathways are implicated.
Insights
Cannabinoid receptor 2 (CB2) ligands, JWH 133 and AM 630, modulate memory and learning in mice. These CB2 receptor interactions show potential for influencing cholinergic pathways implicated in cognitive function.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Cholinergic system dysfunction is linked to Alzheimer's disease (AD).
- The endocannabinoid system (ECS) offers potential therapeutic targets for AD-related memory deficits.
- Cannabinoid receptors, specifically CB1 and CB2, are key components of the ECS.
Purpose of the Study:
- To investigate the impact of selective CB2 receptor ligands on memory and learning in mice.
- To explore the interaction between CB2 receptor modulation and cholinergic pathways in cognitive processes.
Main Methods:
- Utilized the passive avoidance (PA) test to assess memory and learning in mice.
- Administered selective CB2 receptor agonist (JWH 133) and antagonist (AM 630).
- Examined the effects of these ligands in conjunction with cholinergic agonists (nicotine) and antagonists (scopolamine).
Main Results:
- Co-administration of non-effective doses of JWH 133 or AM 630 with nicotine enhanced cognitive performance.
- Neither JWH 133 nor AM 630 alone affected memory enhancement by an effective dose of nicotine.
- Both JWH 133 and AM 630 attenuated scopolamine-induced memory impairment.
Conclusions:
- CB2 receptors play a role in modulating memory-related responses.
- The effects of CB2 receptor ligands are particularly evident in pathways involving cholinergic systems.
- Targeting CB2 receptors may offer a novel strategy for cognitive enhancement in conditions like AD.
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