László Biró1, Zoltán Balogh1, László Szente1, Zoltán Kristóf Varga1, József Haller1, Manó Aliczki1
1 Department of Behavioural Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest 1083, Hungary
Introduction: Endocannabinoid signaling affects behavioral responses to traumatic events, however, the specific roles and possible interactions of the two endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are poorly understood.
Aims: We assessed the specific effects of AEA and 2-AG on acute responses to a traumatic event and consolidation and extinction of traumatic memories.
Methods: Fear conditioning employing electric foot-shocks was followed by seven consecutive daily contextual reminders and a reminder 28 days after conditioning. AEA and 2-AG signalling was enhanced in Wistar rats by pharmacological blockade of their respective degrading enzymes fatty acid amid hydrolase and monoacylglycerol lipase. Systemic treatments were administered before fear conditioning or before the first contextual reminder. Brain site-specific treatments were administered before fear conditioning to the ventral hippocampus (vHC), prelimbic cortex (PrL), basolateral amygdala (BLA).
Results: Acute fear responses were decreased by local enhancement of AEA signalling in the vHC but not in the PrL or BLA, while this effect was inhibited by enhancement of 2-AG signalling. Interestingly, systemic enhancement of 2-AG signalling before fear conditioning decreased acute fear responses and AEA supressed the effects of 2-AG. Local enhancement of AEA in the vHC and PrL led to strong memory consolidation and this effect was inhibited by 2-AG. Enhancement of 2-AG or AEA signalling before the first contextual reminder accelerated traumatic memory extinction.
Conclusion: Taken together, endocannabinoids differentially, interactively regulate behavioural responses to trauma. Acute fear responses are regulated predominantly by 2-AG but under the control of AEA. In the PrL and vHC AEA enhances traumatic memory consolidation under the control of 2-AG but in the BLA AEA inhibits traumatic memory formation. In traumatic memory extinction endocannabinoids have a synergistic role and promote fear relief.
Doctoral School: Neurosciences
Supervisor: Éva Mikics
E-mail address: firstname.lastname@example.org