title: Gene expression of pro-opiomelanocortin and melanocortin receptors is regulated in the hypothalamus and mesocorticolimbic system following nicotine administration.
abstract: Pro-opiomelanocortin (POMC)-derived peptides and their receptors have been shown to play important roles in natural and drug-induced reward and reinforcement. Reward process may involve the regulation of POMC gene expression and the gene expression of POMC-derived peptide receptors. The present study investigated the alterations observed in the transcript levels of POMC, melanocortin 3 (MC3R), melanocortin 4 (MC4R) and mu-opioid receptors (MOR) in the hypothalamus and mesocorticolimbic system during nicotine exposure. Rats were injected subcutaneously for 5days with one of the three doses (0.2, 0.4 or 0.6mg/kg/day, free base) of nicotine and were decapitated one hour after a challenge dose on the sixth day. mRNA levels of POMC in the hypothalamus, MC3R in the ventral tegmental area (VTA), MC4R and MOR in the medial prefrontal cortex (mPFC), nucleus accumbens, dorsal striatum, amygdala, lateral hypothalamic area and VTA were measured by quantitative real-time PCR. Our results showed that treatment with 0.6mg/kg/day nicotine upregulated POMC mRNA in the hypothalamus and MC4R mRNA in the mPFC. Additionally, all three nicotine doses increased MC3R mRNA expression in the VTA. On the other hand, none of the nicotine doses altered MOR mRNA levels in the mesocorticolimbic system and associated limbic structures. These results suggest that nicotine may enhance melanocortin signaling in the mesocorticolimbic system and this alteration may be an important mechanism mediating nicotine reward.
authors.affiliation: Ege University, Institute of Health Sciences, Department of Neuroscience, 35100, Izmir, Turkey. Electronic address: damla1912@gmail.com.
authors.forename: Damla E
authors.initials: DE
authors.lastname: Tapinc
authors.affiliation: Ege University, School of Medicine, Department of Physiology, Izmir, Turkey. Electronic address: ilgin_rabia@hotmail.com.
authors.forename: Rabia
authors.initials: R
authors.lastname: Ilgin
authors.affiliation: Ege University, School of Medicine, Department of Physiology, Izmir, Turkey; Ege University, Center for Brain Research, Izmir, 35100, Turkey. Electronic address: egemen-kaya@hotmail.com.
authors.forename: Egemen
authors.initials: E
authors.lastname: Kaya
authors.affiliation: Ege University, School of Medicine, Department of Physiology, Izmir, Turkey; Ege University, Center for Brain Research, Izmir, 35100, Turkey. Electronic address: oguzgozen@gmail.com.
authors.forename: Oguz
authors.initials: O
authors.lastname: Gozen
authors.affiliation: Ege University, School of Medicine, Department of Physiology, Izmir, Turkey. Electronic address: muzeyyenugur@gmail.com.
authors.forename: Muzeyyen
authors.initials: M
authors.lastname: Ugur
authors.affiliation: Ege University, School of Medicine, Department of Physiology, Izmir, Turkey; Ege University, Center for Brain Research, Izmir, 35100, Turkey. Electronic address: ersin.koylu@gmail.com.
authors.forename: Ersin O
authors.initials: EO
authors.lastname: Koylu
authors.affiliation: Ege University, School of Medicine, Department of Physiology, Izmir, Turkey; Ege University, Center for Brain Research, Izmir, 35100, Turkey. Electronic address: lutfiyekanit@gmail.com.
authors.forename: Lutfiye
authors.initials: L
authors.lastname: Kanit
authors.affiliation: Ege University, School of Medicine, Department of Physiology, Izmir, Turkey; Ege University, Center for Brain Research, Izmir, 35100, Turkey. Electronic address: aysegulkeser@gmail.com.
authors.forename: Aysegul
authors.initials: A
authors.lastname: Keser
authors.affiliation: Ege University, School of Medicine, Department of Physiology, Izmir, Turkey; Ege University, Center for Brain Research, Izmir, 35100, Turkey. Electronic address: burcubalkan69@gmail.com.
authors.forename: Burcu
authors.initials: B
authors.lastname: Balkan
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics*; D017207:Rats, Sprague-Dawley; D044101:Receptors, Melanocortin / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
chemical_list: D044101:Receptors, Melanocortin; D017450:Receptors, Opioid, mu; D011333:Pro-Opiomelanocortin; D009538:Nicotine
keywords: Melanocortin receptor; Mesocorticolimbic system; Nicotine; POMC