Alterations in Phosphorylated CREB Expression in Different Brain Regions following Short- and Long-Term Morphine Exposure: Relationship to Food Intake

Abstract

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. Conclusion. The morphine regulation of P-CREB may explain some of the physiological sequelae of opioid exposure including altered food intake and body weight.

Effects of CCK-8 and GLP-1 on fatty acid sensing and food intake regulation in trout

“…Accordingly, in rainbow trout the phosphorylation status and mRNA abundance of CREB decreased in the hypothalamus and hindbrain after treatment with CCK-8 and GLP-1. This situation is comparable to that observed in mammals under food deprivation (Ren et al 2013) and in fish under anorexigenic conditions such as those elicited by oleate ICV treatment (Conde-Sieira et al 2018). Nevertheless, the phosphorylation status (hypothalamus) and mRNA abundance of FoxO1 (hypothalamus and hindbrain) increased after treatment with CCK-8 and GLP-1.…”

Molecular Changes in Opioid Addiction: The Role of Adenylyl Cyclase and cAMP/PKA System

“…Seven-day treatment with morphine via pellets implantation showed elevated levels of phosphorylated CREB in the lateral hypothalamus, ventral tegmental area (VTA), and the hypothalamus. 59 Alterations in CREB levels were not observed in the NAc and amygdala.…”

“…Phosphorylated CREB levels were not increased in the amygdala with chronic morphine exposure. 59 The role of the central amygdala during the "incubation" phenomenon was examined after chronic morphine administration. Interestingly, animals treated with low but not high doses of morphine exhibited increases in CPP in a three-chambered apparatus after 14 days of withdrawal.…”

Electroacupuncture alleviates retrieval of pain memory and its effect on phosphorylation of cAMP response element-binding protein in anterior cingulate cortex in rats

“…A variety of neuron types,especially the neurons and astrocytes, are able to activate CREB to participate in the formation of synaptic plasticity in the central nervous system and the regulation of physiological and pathological processes [ 12 , 13 ]. The phosphorylation of CREB is directly related to the process of acquisition, consolidation, and retrieval of pain memory [ 14 , 15 ].…”