Figure 3.
Cannabinoid receptor agonist WIN55,212-2 blocks the effects of EP stress on IA conditioning and extinction. a, Before conditioning, rats were microinjected with vehicle (n = 12), placed on the EP (EP Pre-Cond, n = 9), or microinjected with WIN55,212-2 (5 μg/0.5 μl) and immediately afterward placed on the EP (WIN_5+EP, n = 7). The EP Pre-Cond group showed a significantly increased latency to enter the dark side on the first extinction day compared with the vehicle group (Ext1, ap < 0.01). Thus, WIN55,212-2 administered into the BLA before stressor exposure reversed the enhancing effect of the stressor on IA acquisition and/or consolidation. b, Before the first extinction trial, rats were microinjected with vehicle (n = 12), placed on the EP (EP Pre-Ext1, n = 9), or microinjected with WIN55,212-2 (5 μg/0.5 μl) and immediately afterward placed on the EP (WIN_5+EP, n = 10). The EP Pre-Ext1 group showed a significantly increased latency to enter the dark side on the first extinction day (Ext1, ap < 0.05, EP differs from vehicle; bp < 0.01, EP differs from WIN_5+EP). Thus, WIN55,212-2 administered into the BLA before stressor exposure reversed the enhancing effect of the stressor on IA retrieval. c, After the first extinction trial, rats were microinjected with vehicle (n = 14), placed on the EP (EP Post-Ext1, n = 8), or microinjected with WIN55,212-2 (5 μg/0.5 μl) and immediately afterward placed on the EP (WIN_5+EP, n = 8). The EP Post-Ext1 group showed a significantly increased latency to enter the dark side on the second extinction day compared with the other groups (Ext2, ap < 0.05). Thus, WIN55,212-2 administered into the BLA before stressor exposure reversed the disrupting effect of the stressor on IA extinction. d, After the first extinction trial, rats were microinjected with vehicle (n = 8), placed on the EP (EP Post-Ext1, n = 8), or microinjected with a low dose of WIN55,212-2 (2.5 μg/0.5 μl) and immediately afterward placed on the EP (WIN_2.5+EP, n = 8). The EP Post-Ext1 group showed a significantly increased latency to enter the dark side on the second extinction day (Ext2, ap < 0.01, EP Post-Ext1 differs from WIN_2.5+EP). Thus, a lower dose of WIN55,212-2 administered into the BLA before stressor exposure also reversed the disrupting effect of the stressor on IA extinction. e, After the first extinction trial, rats were intraperitoneally injected with vehicle (n = 9), placed on the EP (EP Post-Ext1, n = 8), intraperitoneally injected with WIN (0.25 mg/kg; WIN IP, n = 8), or intraperitoneally injected with WIN and immediately afterward placed on the EP (WIN IP+EP, n = 7). The EP Post-Ext1 group showed a significantly increased latency to enter the dark side on the second extinction day compared with all the other groups (Ext2, ap < 0.01). Thus, intraperitoneal administration of WIN55,212-2 before stressor exposure also reversed the disrupting effect of the stressor on IA extinction.