Journal
JOURNAL OF PSYCHOPHARMACOLOGY
Volume 22, Issue 7, Pages 769-777Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/0269881107083999
Keywords
CB1 receptor; learning; anxiety; hippocampus; amygdala
Funding
- NIH [RO1 NS30219, RO1 DE14625]
- Cellular and Integrative Neuroscience [NS07375]
- Department of Physiology, University of Maryland School of Medicine
Ask authors/readers for more resources
Recently, disruption of the endogenous cannabinoid (endocannabinoid, eCB) system was found to impair extinction in delay and contextual fear conditioning models. However, conditioning procedures used in that work precluded investigation of possible eCB effects on acquisition of learned fear. We therefore examined the role of eCBs in modulating fear responses using multiple-trial versions of trace (hippocampal-dependent) and delay (amygdala-dependent) Pavlovian fear conditioning. By administering the CB1 receptor antagonist AM251 (5 mg/kg, i.p) to C57/Bl/6 mice at various times, we systematically identified the stages of learning and memory (i.e. acquisition, consolidation, recall and extinction) that are modulated by eCB signaling. During tone (CS) - footshock (US) conditioning, AM251 enhanced acquisition of freezing behavior for both trace- and delay-conditioning protocols. CB1 antagonism also enhanced generalized fear (baseline freezing) and cued (CS) freezing during memory recall tests in a state-dependent manner for both trace and delay conditioned animals. Furthermore, in trace- conditioned animals, AM251 impaired extinction performance of both cued and generalized fear. CB1 antagonism did not affect short-term memory (STM) or long-term memory (LTM) consolidation processes. Together, these results suggest that during acquisition and recall of aversive learning, eCBs prevent the expression and retention of inappropriate generalized and learned responses. These findings have important implications for the therapeutic use of CB1 antagonists.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available