title: Changes in phosphorylation of CREB, ERK, and c-fos induction in rat ventral tegmental area, hippocampus and prefrontal cortex after conditioned place preference induced by chemical stimulation of lateral hypothalamus.
abstract: Experimental evidence indicates that chemical stimulation of lateral hypothalamus (LH) by carbachol can produce conditioned place preference (CPP) in rats. Several lines of evidence have shown that cAMP-response element binding protein (CREB), extracellular signal-regulated kinase (ERK), and c-fos have pivotal role in CPP induced by drugs of abuse, such as morphine, cocaine, nicotine, and alcohol. Therefore, in the present study, we investigated the changes in phosphorylated-CREB (p-CREB) and -ERK (p-ERK), and c-fos induction within ventral tegmental area (VTA), hippocampus and prefrontal cortex (PFC) after the acquisition of CPP induced by intra-LH administration of carbachol. Animals were unilaterally implanted by cannula into LH. For chemical stimulation of LH, carbachol (250 nmol/0.5 μl saline) was microinjected once each day, during 3-day conditioning phase (acquisition period) of CPP paradigm. After the acquisition period, the brains were removed, and p-CREB and p-ERK, and c-fos induction in the ipsilateral VTA, hippocampus and PFC were measured by Western blot analysis. The results indicated a significant increase in level of phosphorylated CREB (P<0.01) in VTA, and PFC (P<0.05), during LH stimulation-induced CPP, while its level decreased in hippocampus (P<0.05). Also, in aforementioned regions, an increase in c-fos level was observed, but this enhancement in PFC was not significant. Moreover, p-ERK changed in these areas, but not significantly. Our findings suggest that studying the intracellular signals and their changes, such as phosphorylated-CREB, can elucidate a functional relationship between LH and other brain structures involved in reward processing in rats.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box 19615-1178, Tehran, Iran. Haghparast@yahoo.com
authors.forename: Abbas
authors.initials: A
authors.lastname: Haghparast
authors.forename: Zahra
authors.initials: Z
authors.lastname: Taslimi
authors.forename: Mahmoudreza
authors.initials: M
authors.lastname: Ramin
authors.forename: Pegah
authors.initials: P
authors.lastname: Azizi
authors.forename: Farbia
authors.initials: F
authors.lastname: Khodagholi
authors.forename: Majid
authors.initials: M
authors.lastname: Hassanpour-Ezatti
mesh_terms: D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D050882:CREB-Binding Protein / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D017397:Prefrontal Cortex / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D017557:Ventral Tegmental Area / Q000378:metabolism
chemical_list: D018679:Cholinergic Agonists; D016760:Proto-Oncogene Proteins c-fos; D002217:Carbachol; D050882:CREB-Binding Protein; D048049:Extracellular Signal-Regulated MAP Kinases