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Hippocampus?

Hippocampus?. OR. POST-TRAINING CB1 CANNABINOID RECEPTOR AGONIST ACTIVATION DISRUPTS LONG-TERM CONSOLIDATION OF SPATIAL MEMORIES IN THE HIPPOCAMPUS. T.Yim, N. Hong, M. Ejaredar, J. McKenna, & R. McDonald. Cannabis sativa. Positive effects Euphoria Analgesia

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Hippocampus?

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  1. Hippocampus? OR...

  2. POST-TRAINING CB1 CANNABINOID RECEPTOR AGONISTACTIVATION DISRUPTS LONG-TERM CONSOLIDATION OFSPATIAL MEMORIES IN THE HIPPOCAMPUS T.Yim, N. Hong, M. Ejaredar, J. McKenna, & R. McDonald

  3. Cannabis sativa • Positive effects • Euphoria • Analgesia • Reduction of intraocular pressure • Appetite enhancement • Anti-emetic • Negative effects • Attention and memory deficits • Hallucinations • Respiratory disease

  4. Medical Marijuana

  5. Cannabis sativa • THC (D9-tetrahydrocannabinol) • Equal affinity to CB1R and CB2R • CB2R found in periphery • CB1R found in CNS • Anandamide (N-arachidonylethanolamine)= natural ligand • Made from arachadonic acid • Can be converted to PGF2a • Made in the hippocampus, cortex and cerebellum

  6. THC • Location of CB1R • Hippocampus • Basal ganglia • Substantia nigra

  7. Previous Studies • CB1R activation in dorsal hippocampus impairs spacial memory in rodents • Reversible by CB1R blockade • Not clear which stage is affected • Acquisition, consolidation, or retrieval?

  8. Objective • Determine if cannabinoid activation affects memory consolidation • Activate CB1R after daily training in Morris water maze • Assess spatial recall at various retention intervals

  9. Materials and Methods • 111 male Long-Evans rats • 6 day training in MWM • 1.5 m diameter, .5 m deep • Invisible platform NE quadrant, 28 cm from perimeter • Multiple colored posters in room for cues

  10. Morris water maze

  11. Materials and Methods • Place learning • Training for 6 consecutive days • 8 swimming trials per day • 2 trials from each of 4 starting positions (N, S, E, W) • Trial began when rat was placed in water, ended when rat reached platform or after 60 s

  12. Materials and Methods • Probe test • Invisible platform removed from water maze • Rats placed in pool facing wall from due west • Test begins when rat is released in water and ends after 30 s

  13. Experiment 1 • Systemic injections of WIN • 64 rats assigned to one of four treatment groups • .5mg/kg, 1mg/kg, 3mg/kg, or DMSO(control) • Injections made within 5 min of last swim of each of the 6 training days • Probe test given at two retention periods • 1 week and 4 weeks post-training

  14. Experiment 2 • Intrahippocampal infusions of WIN • All rats received bilateral cannulae implantation to dorsal hippocampus • 47 rats assigned to one of three groups • Control, 2.5ug WIN, 5.0ug WIN • Injections made within 5 min of last swim of each of the 6 training days • Probe test given at two retention periods • 1 week and 4 weeks post-training

  15. Results • Experiment 1

  16. Results • Experiment 1

  17. Results • Experiment 1

  18. Results • Experiment 2

  19. Results • Experiment 2

  20. Results • Experiment 2

  21. Histology • Location of cannulae

  22. Discussion • CB1 agonist WIN impairs consolidation of long term memory • Spares spatial acquisition and short term retention • Consolidation impairment due to CB1R rather than CB2R activation • CB2R not expressed in hippocampus • Isolated consolidation with post-training administration

  23. Discussion • Short-term vs Long-term • NMDA-R blockade in dorsal hippocampus impairs long-term not short-term memory • CB1R activation inhibits long term potentiation • Suppress NMDA-R by inhibiting vg-Ca2+ and activating K+ channels

  24. Discussion • Effects of WIN may be dose dependent • Related to acetylcholine tone • Low dose WIN enhance cholinergic efflux • High dose WIN inhibit cholinergic activity • Low levels of Ach required for memory consolidation during post-training slow-wave sleep

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