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Endocannabinoid modulation of fear responses: learning and state-dependent performance effects.
J Psychopharmacol. 2008 Sep; 22(7):769-77.JP

Abstract

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+Show Affiliations

Department of Physiology, Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA. creich@som.umaryland.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

18308796

Citation

Reich, C G., et al. "Endocannabinoid Modulation of Fear Responses: Learning and State-dependent Performance Effects." Journal of Psychopharmacology (Oxford, England), vol. 22, no. 7, 2008, pp. 769-77.
Reich CG, Mohammadi MH, Alger BE. Endocannabinoid modulation of fear responses: learning and state-dependent performance effects. J Psychopharmacol (Oxford). 2008;22(7):769-77.
Reich, C. G., Mohammadi, M. H., & Alger, B. E. (2008). Endocannabinoid modulation of fear responses: learning and state-dependent performance effects. Journal of Psychopharmacology (Oxford, England), 22(7), 769-77. https://doi.org/10.1177/0269881107083999
Reich CG, Mohammadi MH, Alger BE. Endocannabinoid Modulation of Fear Responses: Learning and State-dependent Performance Effects. J Psychopharmacol (Oxford). 2008;22(7):769-77. PubMed PMID: 18308796.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endocannabinoid modulation of fear responses: learning and state-dependent performance effects. AU - Reich,C G, AU - Mohammadi,M H, AU - Alger,B E, Y1 - 2008/02/28/ PY - 2008/3/1/pubmed PY - 2009/1/7/medline PY - 2008/3/1/entrez SP - 769 EP - 77 JF - Journal of psychopharmacology (Oxford, England) JO - J. Psychopharmacol. (Oxford) VL - 22 IS - 7 N2 - 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. SN - 0269-8811 UR - https://www.unboundmedicine.com/medline/citation/18308796/Endocannabinoid_modulation_of_fear_responses:_learning_and_state_dependent_performance_effects_ L2 - http://journals.sagepub.com/doi/full/10.1177/0269881107083999?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -