1. Hippocampus?
OR...

2. 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

3. Cannabis sativa Positive effects Negative 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