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The effect of CB(1) receptor antagonism in the right basolateral amygdala on conditioned fear and associated analgesia in rats.
Eur J Neurosci. 2007 Nov; 26(9):2643-53.EJ

Abstract

The endocannabinoid system mediates analgesia expressed following exposure to conditioned or unconditioned aversive stimuli, and controls the extinction of conditioned aversive behaviour. The present study investigated the effects of administration of the cannabinoid(1) (CB(1)) receptor antagonist SR141716A into the right basolateral amygdala (BLA) on expression of conditioned fear, formalin-evoked nociceptive behaviour, fear-conditioned analgesia and associated alterations in monoamine levels in discrete rat brain areas. Re-exposure to a context previously paired with footshock significantly reduced formalin-evoked nociceptive behaviour. Intra-BLA administration of SR141716A did not attenuate fear-conditioned analgesia, but reduced formalin-evoked nociceptive behaviour and attenuated the formalin-induced decrease in freezing and 22-kHz ultrasonic vocalizations in the early part of the trial. Furthermore, intra-BLA SR141716A significantly prolonged the duration of these fear-related behaviours in fear-conditioned rats not receiving formalin. Fear-conditioned analgesia was accompanied by increased homovanillic acid (HVA) : dopamine (DA) ratio and reduced serotonin (5-HT) in the cerebellum, an effect not altered by SR141716A. SR141716A-induced analgesia was accompanied by reduced DA, increased HVA : DA ratio and reduced 5-HT levels in the cerebellum, increased hippocampal HVA levels and increased 5-hydroxyindole-3-acetic acid (5-HIAA) in the amygdaloid cortex. The SR141716A-induced prolongation of contextually induced aversive behaviour was accompanied by reduced DA and 3,4-dihydroxyphenylacetic acid (DOPAC), levels in the hippocampus, and increased DA and 5-HIAA in the periaqueductal grey. These data suggest an important role for CB(1) receptors in the right BLA in mediating short-term extinction of conditioned aversive behaviour but not fear-conditioned analgesia. The results also enhance our understanding of endocannabinoid-monoamine interactions of relevance to conditioned fear and associated analgesia.

Authors+Show Affiliations

Department of Pharmacology and Therapeutics, NCBES Neuroscience Cluster and Center for Pain Research, National University of Ireland, Galway, University Road, Galway, Ireland.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17970731

Citation

Roche, Michelle, et al. "The Effect of CB(1) Receptor Antagonism in the Right Basolateral Amygdala On Conditioned Fear and Associated Analgesia in Rats." The European Journal of Neuroscience, vol. 26, no. 9, 2007, pp. 2643-53.
Roche M, O'Connor E, Diskin C, et al. The effect of CB(1) receptor antagonism in the right basolateral amygdala on conditioned fear and associated analgesia in rats. Eur J Neurosci. 2007;26(9):2643-53.
Roche, M., O'Connor, E., Diskin, C., & Finn, D. P. (2007). The effect of CB(1) receptor antagonism in the right basolateral amygdala on conditioned fear and associated analgesia in rats. The European Journal of Neuroscience, 26(9), 2643-53.
Roche M, et al. The Effect of CB(1) Receptor Antagonism in the Right Basolateral Amygdala On Conditioned Fear and Associated Analgesia in Rats. Eur J Neurosci. 2007;26(9):2643-53. PubMed PMID: 17970731.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of CB(1) receptor antagonism in the right basolateral amygdala on conditioned fear and associated analgesia in rats. AU - Roche,Michelle, AU - O'Connor,Emer, AU - Diskin,Catherine, AU - Finn,David P, Y1 - 2007/10/23/ PY - 2007/11/1/pubmed PY - 2008/3/15/medline PY - 2007/11/1/entrez SP - 2643 EP - 53 JF - The European journal of neuroscience JO - Eur. J. Neurosci. VL - 26 IS - 9 N2 - The endocannabinoid system mediates analgesia expressed following exposure to conditioned or unconditioned aversive stimuli, and controls the extinction of conditioned aversive behaviour. The present study investigated the effects of administration of the cannabinoid(1) (CB(1)) receptor antagonist SR141716A into the right basolateral amygdala (BLA) on expression of conditioned fear, formalin-evoked nociceptive behaviour, fear-conditioned analgesia and associated alterations in monoamine levels in discrete rat brain areas. Re-exposure to a context previously paired with footshock significantly reduced formalin-evoked nociceptive behaviour. Intra-BLA administration of SR141716A did not attenuate fear-conditioned analgesia, but reduced formalin-evoked nociceptive behaviour and attenuated the formalin-induced decrease in freezing and 22-kHz ultrasonic vocalizations in the early part of the trial. Furthermore, intra-BLA SR141716A significantly prolonged the duration of these fear-related behaviours in fear-conditioned rats not receiving formalin. Fear-conditioned analgesia was accompanied by increased homovanillic acid (HVA) : dopamine (DA) ratio and reduced serotonin (5-HT) in the cerebellum, an effect not altered by SR141716A. SR141716A-induced analgesia was accompanied by reduced DA, increased HVA : DA ratio and reduced 5-HT levels in the cerebellum, increased hippocampal HVA levels and increased 5-hydroxyindole-3-acetic acid (5-HIAA) in the amygdaloid cortex. The SR141716A-induced prolongation of contextually induced aversive behaviour was accompanied by reduced DA and 3,4-dihydroxyphenylacetic acid (DOPAC), levels in the hippocampus, and increased DA and 5-HIAA in the periaqueductal grey. These data suggest an important role for CB(1) receptors in the right BLA in mediating short-term extinction of conditioned aversive behaviour but not fear-conditioned analgesia. The results also enhance our understanding of endocannabinoid-monoamine interactions of relevance to conditioned fear and associated analgesia. SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/17970731/The_effect_of_CB_1__receptor_antagonism_in_the_right_basolateral_amygdala_on_conditioned_fear_and_associated_analgesia_in_rats_ L2 - https://doi.org/10.1111/j.1460-9568.2007.05861.x DB - PRIME DP - Unbound Medicine ER -