Alterations in phosphorylated CREB expression in different brain regions following short- and long-term morphine exposure: relationship to food intake.
BACKGROUND
Activation of the cyclic adenosine monophosphate (cAMP)/phosphorylated CREB (P-CREB) system in different brain regions has been implicated in mediating opioid tolerance and dependence, while alteration of this system in the lateral hypothalamus (LH) has been suggested to have a role in food intake and body weight.


METHODS
Given that opioids regulate food intake, we measured P-CREB in different brain regions in mice exposed to morphine treatments designed to induce different degrees of tolerance and dependence.


RESULTS
We found that a single morphine injection or daily morphine injections for 8 days did not influence P-CREB levels, while the escalating dose of morphine regimen raised P-CREB levels only in the ventral tegmental area (VTA). Chronic morphine pellet implantation for 7 days raised P-CREB levels in the LH, VTA, and dorsomedial nucleus of the hypothalamus (DM) but not in the nucleus accumbens and amygdala. Increased P-CREB levels in LH, VTA, and DM following 7-day treatment with morphine pellets and increased P-CREB levels in the VTA following escalating doses of morphine were associated with decreased food intake and body weight.


CONCLUSIONS
The morphine regulation of P-CREB may explain some of the physiological sequelae of opioid exposure including altered food intake and body weight.
Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Charles R. Drew University of Medicine and Science and UCLA School of Medicine, 1731 E. 120th. Street, Los Angeles, CA 90059, USA.
Xiuhai
X
Ren
Kabirullah
K
Lutfy
Michael
M
Mangubat
Monica G
MG
Ferrini
Martin L
ML
Lee
Yanjun
Y
Liu
Theodore C
TC
Friedman
D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004343:Drug Implants; D004435:Eating / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects*; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000008:administration & dosage*; D009021:Morphine Dependence / Q000378:metabolism* / Q000523:psychology; D009292:Narcotic Antagonists / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects; D010766:Phosphorylation; D013375:Substance Withdrawal Syndrome / Q000378:metabolism / Q000523:psychology; D013997:Time Factors
D000701:Analgesics, Opioid; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D004343:Drug Implants; D009292:Narcotic Antagonists; D009020:Morphine