Abstract
Opioid addiction is recognized as a chronic relapsing brain disease resulting from repeated exposure to opioid drugs. Cellular and molecular mechanisms underlying the ability of organism to return back to the physiological norm after cessation of drug supply are not fully understood. The aim of this work was to extend our previous studies of morphine-induced alteration of rat forebrain cortex protein composition to the hippocampus. Rats were exposed to morphine for 10 days and sacrificed 24 h (groups +M10 and −M10) or 20 days after the last dose of morphine (groups +M10/−M20 and −M10/−M20). The six altered proteins (≥2-fold) were identified in group (+M10) when compared with group (−M10) by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE). The number of differentially expressed proteins was increased to thirteen after 20 days of the drug withdrawal. Noticeably, the altered level of α-synuclein, β-synuclein, α-enolase and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was also determined in both (±M10) and (±M10/−M20) samples of hippocampus. Immunoblot analysis of 2D gels by specific antibodies oriented against α/β-synucleins and GAPDH confirmed the data obtained by 2D-DIGE analysis. Label-free quantification identified nineteen differentially expressed proteins in group (+M10) when compared with group (−M10). After 20 days of morphine withdrawal (±M10/−M20), the number of altered proteins was increased to twenty. We conclude that the morphine-induced alteration of protein composition in rat hippocampus after cessation of drug supply proceeds in a different manner when compared with the forebrain cortex. In forebrain cortex, the total number of altered proteins was decreased after 20 days without morphine, whilst in hippocampus, it was increased.
Highlights
Opioid dependence and withdrawal syndrome are the leading problems associated with licit and illicit opioid use
In accordance with the data of Sim et al [3], Sim-Selley et al [4] and Maher et al [5], indicated a desensitization of (2-D-alanine2-4-methylphenylalanine-5-glycineol)-enkephalin (DAMGO)- and (2-D-alanine-5-D-leucine)-enkephalin (DADLE)-stimulated G-protein responses in plasma membranes (PM) isolated from forebrain cortex (FBC) of rats exposed to morphine for 10 days [6]
Comparative proteomic analysis of rat hippocampus from animals exposed to morphine for 10 days (+M10) and from control animals (−M10) by 2D-DIGE and MALDI-TOF MS/MS
Summary
Opioid dependence and withdrawal syndrome are the leading problems associated with licit and illicit opioid use. Proteomic analysis of rat hippocampus exposed to morphine treatment and 20-day drug withdrawal available information about the durability and reversibility of potentially adverse effects of opioid treatment and withdrawal. From a clinical point of view, drug withdrawal is the leading pathophysiological state driving opioid dependence and addictive behaviors [1,2]. Behavioral tests proved that these rats developed a tolerance to this drug as there was no significant difference between control (−M10) and morphine-treated (+M10) rats in the sensitivity to heat stimulation (hot-plate test), which was determined as a delay in hind paw withdrawal. Precipitation of morphine withdrawal state by naloxone resulted in a rapid and dramatic opiate abstinence syndrome. There were no detectable signs of abstinence syndrome (such as body shakes, teeth clatter, vacuous chewing, ptosis, irritability to touch, diarrhea), in the (−M10) animals
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