title: Decreased Caffeine-Induced Locomotor Activity via Microinjection of CART Peptide into the Nucleus Accumbens Is Linked to Inhibition of the pCaMKIIa-D3R Interaction.
abstract: The purpose of this study was to characterize the inhibitory modulation of cocaine- and amphetamine-regulated transcript (CART) peptides, particularly with respect to the function of the D3 dopamine receptor (D3R), which is activated by its interaction with phosphorylated CaMKIIα (pCaMKIIα) in the nucleus accumbens (NAc). After repeated oral administration of caffeine (30 mg/kg) for five days, microinjection of CART peptide (0.08 μM/0.5 μl/hemisphere) into the NAc affected locomotor behavior. The pCaMKIIα-D3R interaction, D3R phosphorylation and cAMP/PKA/phosphorylated CREB (pCREB) signaling pathway activity were measured in NAc tissues, and Ca2+ influx and pCaMKIIα levels were measured in cultured NAc neurons. We found that CART attenuated the caffeine-mediated enhancement of depolarization-induced Ca2+ influx and CaMKIIα phosphorylation in cultured NAc neurons. Repeated microinjection of CART peptides into the NAc decreased the caffeine-induced enhancement of Ca2+ channels activity, pCaMKIIα levels, the pCaMKIIα-D3R interaction, D3R phosphorylation, cAMP levels, PKA activity and pCREB levels in the NAc. Furthermore, behavioral sensitization was observed in rats that received five-day administration of caffeine following microinjection of saline but not in rats that were treated with caffeine following microinjection of CART peptide. These results suggest that caffeine-induced CREB phosphorylation in the NAc was ameliorated by CART peptide due to its inhibition of D3R phosphorylation. These effects of CART peptides may play a compensatory role by inhibiting locomotor behavior in rats.
authors.affiliation: Department of Respiration, The Fourth Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China.|Department of Respiration, Department Two, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Pathophysiology, College of Medicine, Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Breast Surgery, Jiangxi Tumor Hospital, Nanchang, Jiangxi, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Pathophysiology, College of Medicine, Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Physiology, College of Medicine, Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yang
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Ki-Wan
authors.initials: KW
authors.lastname: Oh
authors.affiliation: Department of Pathophysiology, College of Medicine, Nanchang University, Nanchang, Jiangxi, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000818:Animals; D002110:Caffeine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D050637:Receptors, Dopamine D3; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D002110:Caffeine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium