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The endocannabinoid transport inhibitor AM404 modulates nociception in cholestasis.
Neurosci Lett. 2009 Oct 25; 462(3):230-4.NL

Abstract

Cholestasis is associated with increased activity of the endogenous opioid system that results in analgesia. Endocannabinoid system can reduce pain sensitivity. Considering the interaction that has been shown between the endogenous opioid and endocannabinoid systems in nociception processing, we studied the effect of AM404, an endocannabinoid transport inhibitor, on modulation of nociception in cholestasis, a model of elevated endogenous opioid tone. Cholestasis was induced by ligation of the main bile duct using two ligatures and transection of the duct at the midpoint between them. A significant increase (P<0.01) in TF was observed in cholestatic rats compared to unoperated and sham rats. AM404 (10 mg/kg, i.p.) significantly increased TFL at 5, 30 min but not 60 min after injection in cholestatic animals compared to the vehicle treated cholestatic group (P<0.05, P<0.001, respectively). AM404 injection to unoperated and sham rats did not alter baseline TFL. The effect of AM404 in cholestatic rats was blocked by co-administration of a CB(1) receptor antagonist, AM251 (1 mg/kg, i.p.) but not by the CB2 receptor antagonist, SR144528 (1 mg/kg, i.p.). Naloxone injection blocked the antinociception induced by cholestasis in bile duct ligated group. Antinociception produced by injection of AM404 in cholestatics was also attenuated by co-administration of naloxone. These data show that AM404 potentiates antinociception induced by cholestasis and indicate that there are possible interactions between opioid and cannabinoid systems in this experimental model of elevated endogenous opioid tone. The inhibitory effects of AM404 in this model are mediated by cannabinoid CB(1) and not CB(2) receptors.

Authors+Show Affiliations

Department of Biology, School of Basic Sciences, Bu-Ali Sina University, Hamadan, Iran. p.hasanein@basu.ac.ir

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19616063

Citation

Hasanein, Parisa. "The Endocannabinoid Transport Inhibitor AM404 Modulates Nociception in Cholestasis." Neuroscience Letters, vol. 462, no. 3, 2009, pp. 230-4.
Hasanein P. The endocannabinoid transport inhibitor AM404 modulates nociception in cholestasis. Neurosci Lett. 2009;462(3):230-4.
Hasanein, P. (2009). The endocannabinoid transport inhibitor AM404 modulates nociception in cholestasis. Neuroscience Letters, 462(3), 230-4. https://doi.org/10.1016/j.neulet.2009.07.026
Hasanein P. The Endocannabinoid Transport Inhibitor AM404 Modulates Nociception in Cholestasis. Neurosci Lett. 2009 Oct 25;462(3):230-4. PubMed PMID: 19616063.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The endocannabinoid transport inhibitor AM404 modulates nociception in cholestasis. A1 - Hasanein,Parisa, Y1 - 2009/07/16/ PY - 2009/04/08/received PY - 2009/07/08/revised PY - 2009/07/10/accepted PY - 2009/7/21/entrez PY - 2009/7/21/pubmed PY - 2009/10/27/medline SP - 230 EP - 4 JF - Neuroscience letters JO - Neurosci. Lett. VL - 462 IS - 3 N2 - Cholestasis is associated with increased activity of the endogenous opioid system that results in analgesia. Endocannabinoid system can reduce pain sensitivity. Considering the interaction that has been shown between the endogenous opioid and endocannabinoid systems in nociception processing, we studied the effect of AM404, an endocannabinoid transport inhibitor, on modulation of nociception in cholestasis, a model of elevated endogenous opioid tone. Cholestasis was induced by ligation of the main bile duct using two ligatures and transection of the duct at the midpoint between them. A significant increase (P<0.01) in TF was observed in cholestatic rats compared to unoperated and sham rats. AM404 (10 mg/kg, i.p.) significantly increased TFL at 5, 30 min but not 60 min after injection in cholestatic animals compared to the vehicle treated cholestatic group (P<0.05, P<0.001, respectively). AM404 injection to unoperated and sham rats did not alter baseline TFL. The effect of AM404 in cholestatic rats was blocked by co-administration of a CB(1) receptor antagonist, AM251 (1 mg/kg, i.p.) but not by the CB2 receptor antagonist, SR144528 (1 mg/kg, i.p.). Naloxone injection blocked the antinociception induced by cholestasis in bile duct ligated group. Antinociception produced by injection of AM404 in cholestatics was also attenuated by co-administration of naloxone. These data show that AM404 potentiates antinociception induced by cholestasis and indicate that there are possible interactions between opioid and cannabinoid systems in this experimental model of elevated endogenous opioid tone. The inhibitory effects of AM404 in this model are mediated by cannabinoid CB(1) and not CB(2) receptors. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/19616063/The_endocannabinoid_transport_inhibitor_AM404_modulates_nociception_in_cholestasis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(09)00947-1 DB - PRIME DP - Unbound Medicine ER -