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Modulatory role of the intra-accumbal CB1 receptor in protein level of the c-fos and pCREB/CREB ratio in the nucleus accumbens and ventral tegmental area in extinction and morphine seeking in the rats.
Brain Res Bull. 2018 09; 142:320-327.BR

Abstract

Brain reward and motivation circuit begin from the ventral tegmental area (VTA) that its dopaminergic terminals project to various regions of the brain including the nucleus accumbens (NAc). This reward circuit is influenced by drugs of abuse such as morphine and cannabinoid. The present study tried to investigate the role of the intra-accumbal CB1 receptor in the c-fos level and pCREB/CREB ratio in the NAc and the VTA during reinstatement phase of morphine-induced conditioned place preference (CPP) by western blotting. The present data reveals that intra-accumbal administration of CB1 agonist, WIN55,212-2 (0.5, 1 and 2 mM/0.5 μl DMSO) before/during extinction period of morphine-induced CPP, significantly decreased the NAc and the VTA c-fos protein level in the reinstatement phase; whereas the pre-reinstatement administration of the CB1 agonist, increased the c-fos protein level. Intra-accumbal administration of the CB1 agonist during the extinction period of morphine-induced CPP reduced the pCREB/CREB ratio in the NAc. Also, the present data show that intra-accumbal administration of CB1 antagonist, AM251 (15, 45 and 90 μM/0.5 μl DMSO) during/after extinction period of morphine-induced CPP affects the NAc and the VTA c-fos protein level in the reinstatement phase. Also, intra-NAc microinjection of AM251 during the extinction period reduced pCREB/CREB ratio in these regions. In conclusion, the results presented here provide compelling evidence of the modulation and involvement of the c-fos and the CREB molecules in the cannabinoid-opioid interaction of the brain reward system in the CPP paradigm.

Authors+Show Affiliations

Department of Physiology, School of Medicine, Babol University of Medical Sciences, Babol, Iran; Neuroscience Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, P.O. Box 19615-1178, Tehran, Iran.Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran; Department of Neuroscience, University of Florida College of Medicine and McKnight Brain Institute, Gainesville, FL, 32610, USA.Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, P.O. Box 19615-1178, Tehran, Iran. Electronic address: Haghparast@sbmu.ac.ir.

Pub Type(s)

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

Language

eng

PubMed ID

30170186

Citation

Khaleghzadeh-Ahangar, Hossein, et al. "Modulatory Role of the Intra-accumbal CB1 Receptor in Protein Level of the C-fos and pCREB/CREB Ratio in the Nucleus Accumbens and Ventral Tegmental Area in Extinction and Morphine Seeking in the Rats." Brain Research Bulletin, vol. 142, 2018, pp. 320-327.
Khaleghzadeh-Ahangar H, Khodagholi F, Shaerzadeh F, et al. Modulatory role of the intra-accumbal CB1 receptor in protein level of the c-fos and pCREB/CREB ratio in the nucleus accumbens and ventral tegmental area in extinction and morphine seeking in the rats. Brain Res Bull. 2018;142:320-327.
Khaleghzadeh-Ahangar, H., Khodagholi, F., Shaerzadeh, F., & Haghparast, A. (2018). Modulatory role of the intra-accumbal CB1 receptor in protein level of the c-fos and pCREB/CREB ratio in the nucleus accumbens and ventral tegmental area in extinction and morphine seeking in the rats. Brain Research Bulletin, 142, 320-327. https://doi.org/10.1016/j.brainresbull.2018.08.017
Khaleghzadeh-Ahangar H, et al. Modulatory Role of the Intra-accumbal CB1 Receptor in Protein Level of the C-fos and pCREB/CREB Ratio in the Nucleus Accumbens and Ventral Tegmental Area in Extinction and Morphine Seeking in the Rats. Brain Res Bull. 2018;142:320-327. PubMed PMID: 30170186.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulatory role of the intra-accumbal CB1 receptor in protein level of the c-fos and pCREB/CREB ratio in the nucleus accumbens and ventral tegmental area in extinction and morphine seeking in the rats. AU - Khaleghzadeh-Ahangar,Hossein, AU - Khodagholi,Fariba, AU - Shaerzadeh,Fatemeh, AU - Haghparast,Abbas, Y1 - 2018/08/28/ PY - 2018/04/19/received PY - 2018/06/26/revised PY - 2018/08/25/accepted PY - 2018/9/1/pubmed PY - 2019/7/31/medline PY - 2018/9/1/entrez KW - CB1 receptor KW - CREB KW - Morphine KW - Nucleus accumbens KW - Ventral tegmental area KW - c-fos SP - 320 EP - 327 JF - Brain research bulletin JO - Brain Res Bull VL - 142 N2 - Brain reward and motivation circuit begin from the ventral tegmental area (VTA) that its dopaminergic terminals project to various regions of the brain including the nucleus accumbens (NAc). This reward circuit is influenced by drugs of abuse such as morphine and cannabinoid. The present study tried to investigate the role of the intra-accumbal CB1 receptor in the c-fos level and pCREB/CREB ratio in the NAc and the VTA during reinstatement phase of morphine-induced conditioned place preference (CPP) by western blotting. The present data reveals that intra-accumbal administration of CB1 agonist, WIN55,212-2 (0.5, 1 and 2 mM/0.5 μl DMSO) before/during extinction period of morphine-induced CPP, significantly decreased the NAc and the VTA c-fos protein level in the reinstatement phase; whereas the pre-reinstatement administration of the CB1 agonist, increased the c-fos protein level. Intra-accumbal administration of the CB1 agonist during the extinction period of morphine-induced CPP reduced the pCREB/CREB ratio in the NAc. Also, the present data show that intra-accumbal administration of CB1 antagonist, AM251 (15, 45 and 90 μM/0.5 μl DMSO) during/after extinction period of morphine-induced CPP affects the NAc and the VTA c-fos protein level in the reinstatement phase. Also, intra-NAc microinjection of AM251 during the extinction period reduced pCREB/CREB ratio in these regions. In conclusion, the results presented here provide compelling evidence of the modulation and involvement of the c-fos and the CREB molecules in the cannabinoid-opioid interaction of the brain reward system in the CPP paradigm. SN - 1873-2747 UR - https://www.unboundmedicine.com/medline/citation/30170186/Modulatory_role_of_the_intra_accumbal_CB1_receptor_in_protein_level_of_the_c_fos_and_pCREB/CREB_ratio_in_the_nucleus_accumbens_and_ventral_tegmental_area_in_extinction_and_morphine_seeking_in_the_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0361-9230(18)30294-6 DB - PRIME DP - Unbound Medicine ER -