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Activation of endocannabinoid transmission induces antidepressant-like effects in rats.
J Physiol Pharmacol 2008; 59(2):217-28JP

Abstract

Recent reports indicate that endocannabinoid (eCB) system may be involved in depression and in the antidepressant-like activity demonstrated in experimental models. The present study examined the effects of the eCB uptake inhibitor 4-hydroxyphenyl-5Z,8Z,11Z,14Z-eicosatetraenamide (AM404; 0.1-3 mg/kg), the fatty acid amide hydrolase (FAAH) inhibitor cyclohexylcarbamic acid 3-carbamoylbiphenyl-3-yl ester (URB597; 0.03-0.3 mg/kg), the cannabinoid CB(1) receptor agonist (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl) phenyl]-trans-4-(3-hydroxypropyl)-cyclohexanol (CP55,940; 0.03-0.3 mg/kg) and the CB(1) receptor antagonist rimonabant (0.3-3 mg/kg) on immobility time in the forced swim test (FST) in rats. Moreover, the effects of AM404, CP55,940 and URB597 on the antidepressant-like activity of imipramine and citalopram in the FST were also examined. We found that AM404 (0.3-3 mg/kg), CP55,940 (0.1 mg/kg) and URB597 (0.1-0.3 mg/kg) reduced the immobility time of rats, while rimonabant (0.3-3 mg/kg) was inactive in this respect. We also observed that the anti-immobility effects of AM404 (1 mg/kg), CP55,940 (0.1 mg/kg) and URB597 (0.3 mg/kg), but not of imipramine (30 mg/kg), were blocked by rimonabant (3 mg/kg). In another set of experiments we showed that the inactive dose of AM404 (0.1 mg/kg) potentiated the effects of the inactive doses of imipramine (15 mg/kg) or citalopram (30 mg/kg), while CP55,940 (0.03 mg/kg) and URB597 (0.03 mg/kg) enhanced the effect of imipramine only. None of the drugs studied, given alone or in combination, increased the basal locomotor activity of rats. Our results indicate that activation of the eCB system induces antidepressant-like effects in the FST in rats, and that these effects are mediated by CB(1) receptors. Moreover, they also indicate that agents activating eCB transmission enhance the anti-immobility responses to antidepressant drugs.

Authors+Show Affiliations

Laboratory of Drug Addiction Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Kraków, Poland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18622041

Citation

Adamczyk, P, et al. "Activation of Endocannabinoid Transmission Induces Antidepressant-like Effects in Rats." Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, vol. 59, no. 2, 2008, pp. 217-28.
Adamczyk P, Gołda A, McCreary AC, et al. Activation of endocannabinoid transmission induces antidepressant-like effects in rats. J Physiol Pharmacol. 2008;59(2):217-28.
Adamczyk, P., Gołda, A., McCreary, A. C., Filip, M., & Przegaliński, E. (2008). Activation of endocannabinoid transmission induces antidepressant-like effects in rats. Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, 59(2), pp. 217-28.
Adamczyk P, et al. Activation of Endocannabinoid Transmission Induces Antidepressant-like Effects in Rats. J Physiol Pharmacol. 2008;59(2):217-28. PubMed PMID: 18622041.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of endocannabinoid transmission induces antidepressant-like effects in rats. AU - Adamczyk,P, AU - Gołda,A, AU - McCreary,A C, AU - Filip,M, AU - Przegaliński,E, PY - 2007/12/12/received PY - 2008/04/25/accepted PY - 2008/7/16/pubmed PY - 2008/12/17/medline PY - 2008/7/16/entrez SP - 217 EP - 28 JF - Journal of physiology and pharmacology : an official journal of the Polish Physiological Society JO - J. Physiol. Pharmacol. VL - 59 IS - 2 N2 - Recent reports indicate that endocannabinoid (eCB) system may be involved in depression and in the antidepressant-like activity demonstrated in experimental models. The present study examined the effects of the eCB uptake inhibitor 4-hydroxyphenyl-5Z,8Z,11Z,14Z-eicosatetraenamide (AM404; 0.1-3 mg/kg), the fatty acid amide hydrolase (FAAH) inhibitor cyclohexylcarbamic acid 3-carbamoylbiphenyl-3-yl ester (URB597; 0.03-0.3 mg/kg), the cannabinoid CB(1) receptor agonist (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl) phenyl]-trans-4-(3-hydroxypropyl)-cyclohexanol (CP55,940; 0.03-0.3 mg/kg) and the CB(1) receptor antagonist rimonabant (0.3-3 mg/kg) on immobility time in the forced swim test (FST) in rats. Moreover, the effects of AM404, CP55,940 and URB597 on the antidepressant-like activity of imipramine and citalopram in the FST were also examined. We found that AM404 (0.3-3 mg/kg), CP55,940 (0.1 mg/kg) and URB597 (0.1-0.3 mg/kg) reduced the immobility time of rats, while rimonabant (0.3-3 mg/kg) was inactive in this respect. We also observed that the anti-immobility effects of AM404 (1 mg/kg), CP55,940 (0.1 mg/kg) and URB597 (0.3 mg/kg), but not of imipramine (30 mg/kg), were blocked by rimonabant (3 mg/kg). In another set of experiments we showed that the inactive dose of AM404 (0.1 mg/kg) potentiated the effects of the inactive doses of imipramine (15 mg/kg) or citalopram (30 mg/kg), while CP55,940 (0.03 mg/kg) and URB597 (0.03 mg/kg) enhanced the effect of imipramine only. None of the drugs studied, given alone or in combination, increased the basal locomotor activity of rats. Our results indicate that activation of the eCB system induces antidepressant-like effects in the FST in rats, and that these effects are mediated by CB(1) receptors. Moreover, they also indicate that agents activating eCB transmission enhance the anti-immobility responses to antidepressant drugs. SN - 1899-1505 UR - https://www.unboundmedicine.com/medline/citation/18622041/Activation_of_endocannabinoid_transmission_induces_antidepressant_like_effects_in_rats_ L2 - http://www.jpp.krakow.pl/journal/archive/06_08/pdf/217_06_08_article.pdf DB - PRIME DP - Unbound Medicine ER -