Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4313779 | Behavioural Brain Research | 2011 | 7 Pages |
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.
Research highlights► p-CREB in the VTA and PFC significantly increased after LH stimulation-induced CPP. ► LH stimulation-induced CPP could decrease CREB phosphorylation in the hippocampus. ► There was no significant change in p-ERK after CPP in the VTA, hippocampus and PFC. ► After LH stimulation-induced CPP, c-fos induction increased in these three regions.