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FACILITATION OF CONTEXTUAL FEAR MEMORY EXTINCTION AND ANTI-ANXIOGENIC EFFECTS OF AM404 AND CANNABIDIOL IN CONDITIONED RATS Fabrício Pamplona, on behalf of Prof. Reinaldo N. Takahashi Depto. de Farmacologia, CCB, UFSC, Florianópolis – SC, Brazil Therapeutic Potential of the Cannabinoids: Present and Future
[object Object],[object Object],[object Object],Patel and Hillard (2006) C A N N A B I N O I D S  vs  A N X I E T Y
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Yehuda (2002) A N X I E T Y
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Yehuda (2002) A N X I E T Y
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Limited pharmacotherapy (5HT re-uptake inhibitors) Association with exposure-based  psychotherapies Yehuda (2002) A N X I E T Y
Conditioned fear responses have been extensively used to understand how aversive memories are formed and as putative animal models of disorders such as PTSD. Conditioned fear PTSD C O N T E X T U A L  F E A R  vs  P T S D
C A N N A B I N O I D S  AND  FEAR  M E M O R I E S
Pacher et al (2006) C A N N A B I N O I D S  USED
Pacher et al (2006) C A N N A B I N O I D S  USED
stereotaxic surgery Day 1 (conditioning) : 3 min    shock (1.5 mA, 1s)    1 min Day 2-4 (extinction) :  9 min context exposure. 3 X at 24 h intervals Freezing evaluation Day 5 (drug-free test) : 3 min context exposure Freezing evaluation C O N T E X T U A L  F E A R  C O N D I T I O N I N G
Experiment 1 : AM404 (0.2, 1, 2 ug/uL, i.c.v.), CBD (0.2, 1, 2 ug/uL, i.c.v.) or control (10% DMSO) 5min before extinction sessions Experiment 2 : SR141716A (0.2 mg/kg, i.p.) 20 min before  AM404 or CBD i.c.v. injections Experiment 3 : Capsazepine (5 ug/uL, i.c.v.) 5 min before  AM404 or CBD i.c.v. injections stereotaxic surgery Day 1 (conditioning) : 3 min    shock (1.5 mA, 1s)    1 min Day 2-4 (extinction) :  9 min context exposure. 3 X at 24 h intervals Day 5 (drug free test) : 3 min context exposure Freezing evaluation Freezing evaluation C O N T E X T U A L  F E A R  C O N D I T I O N I N G
Experiment 1: Effects of AM404 and CBD on contextual fear  extinction R E S U L T S
Experiment 2: Role of CB 1  cannabinoid receptors R E S U L T S
Experiment 3: Role of TRPV 1  vanilloid receptors R E S U L T S
Possible contribution of anxiolytic-like effects? R E S U L T S
Experiment 4: Effects of DZP on contextual fear extinction R E S U L T S
Experiment 5: Effects of AM404, CBD and DZP in the fear-potentiated EPM test. R E S U L T S
Experiment 5: Effects of AM404, CBD and DZP in the fear-potentiated EPM test. R E S U L T S
Experiment 5: Effects of AM404, CBD and DZP in the fear-potentiated EPM test. R E S U L T S
Experiment 5: Effects of AM404, CBD and DZP in the fear-potentiated EPM test. R E S U L T S
[object Object],[object Object],[object Object],[object Object],C O N C L U S I O N S
Rafael Bitencourt PhD student Fabrício Pamplona PhD student Prof. Dr. Reinaldo N. Takahashi CANNABINOID BOYS A C K N O W L E D G E M E N T S Hi Rik, Thanks a lot for your help Muito Obrigado!

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ICRS Sat 2008

  • 1. FACILITATION OF CONTEXTUAL FEAR MEMORY EXTINCTION AND ANTI-ANXIOGENIC EFFECTS OF AM404 AND CANNABIDIOL IN CONDITIONED RATS Fabrício Pamplona, on behalf of Prof. Reinaldo N. Takahashi Depto. de Farmacologia, CCB, UFSC, Florianópolis – SC, Brazil Therapeutic Potential of the Cannabinoids: Present and Future
  • 2.
  • 3.
  • 4.
  • 5.
  • 6. Conditioned fear responses have been extensively used to understand how aversive memories are formed and as putative animal models of disorders such as PTSD. Conditioned fear PTSD C O N T E X T U A L F E A R vs P T S D
  • 7. C A N N A B I N O I D S AND FEAR M E M O R I E S
  • 8. Pacher et al (2006) C A N N A B I N O I D S USED
  • 9. Pacher et al (2006) C A N N A B I N O I D S USED
  • 10. stereotaxic surgery Day 1 (conditioning) : 3 min  shock (1.5 mA, 1s)  1 min Day 2-4 (extinction) : 9 min context exposure. 3 X at 24 h intervals Freezing evaluation Day 5 (drug-free test) : 3 min context exposure Freezing evaluation C O N T E X T U A L F E A R C O N D I T I O N I N G
  • 11. Experiment 1 : AM404 (0.2, 1, 2 ug/uL, i.c.v.), CBD (0.2, 1, 2 ug/uL, i.c.v.) or control (10% DMSO) 5min before extinction sessions Experiment 2 : SR141716A (0.2 mg/kg, i.p.) 20 min before AM404 or CBD i.c.v. injections Experiment 3 : Capsazepine (5 ug/uL, i.c.v.) 5 min before AM404 or CBD i.c.v. injections stereotaxic surgery Day 1 (conditioning) : 3 min  shock (1.5 mA, 1s)  1 min Day 2-4 (extinction) : 9 min context exposure. 3 X at 24 h intervals Day 5 (drug free test) : 3 min context exposure Freezing evaluation Freezing evaluation C O N T E X T U A L F E A R C O N D I T I O N I N G
  • 12. Experiment 1: Effects of AM404 and CBD on contextual fear extinction R E S U L T S
  • 13. Experiment 2: Role of CB 1 cannabinoid receptors R E S U L T S
  • 14. Experiment 3: Role of TRPV 1 vanilloid receptors R E S U L T S
  • 15. Possible contribution of anxiolytic-like effects? R E S U L T S
  • 16. Experiment 4: Effects of DZP on contextual fear extinction R E S U L T S
  • 17. Experiment 5: Effects of AM404, CBD and DZP in the fear-potentiated EPM test. R E S U L T S
  • 18. Experiment 5: Effects of AM404, CBD and DZP in the fear-potentiated EPM test. R E S U L T S
  • 19. Experiment 5: Effects of AM404, CBD and DZP in the fear-potentiated EPM test. R E S U L T S
  • 20. Experiment 5: Effects of AM404, CBD and DZP in the fear-potentiated EPM test. R E S U L T S
  • 21.
  • 22. Rafael Bitencourt PhD student Fabrício Pamplona PhD student Prof. Dr. Reinaldo N. Takahashi CANNABINOID BOYS A C K N O W L E D G E M E N T S Hi Rik, Thanks a lot for your help Muito Obrigado!