Chronic Nicotine Treatment Impacts the Regulation of Opioid and Non-opioid Peptides in the Rat Dorsal Striatum

Abstract

The chronic use of nicotine, the main psychoactive ingredient of tobacco smoking, alters diverse physiological processes and consequently generates physical dependence. To understand the impact of chronic nicotine on neuropeptides, which are potential molecules associated with dependence, we conducted qualitative and quantitative neuropeptidomics on the rat dorsal striatum, an important brain region implicated in the preoccupation/ craving phase of drug dependence. We used extensive LC-FT-MS/MS analyses for neuropeptide identification and LC-FT-MS in conjunction with stable isotope addition for relative quantification. The treatment with chronic nicotine for 3 months led to moderate changes in the levels of endogenous dorsal striatum peptides. Five enkephalin opioid peptides were up-regulated, although no change was observed for dynorphin peptides. Specially, nicotine altered levels of nine non-opioid peptides derived from precursors, including somatostatin and cerebellin, which potentially modulate neurotransmitter release and energy metabolism. This broad but selective impact on the multiple peptidergic systems suggests that apart from the opioid peptides, several other peptidergic systems are involved in the preoccupation/craving phase of drug dependence. Our finding permits future evaluation of the neurochemical circuits modulated by chronic nicotine exposure and provides a number of novel molecules that could serve as potential therapeutic targets for treating drug dependence. Molecular & Cellular

Stress Impacts the Regulation Neuropeptides in the Rat Hippocampus and Prefrontal Cortex

“…The neuropeptides were extracted using a dual phase method for mixing on column (MOC) analysis as introduced in our previous publication . To minimize interference from protein fragmentation, temperature was controlled during all extraction procedures .…”

“…The extracts of hippocampus and PFC were analyzed on a LTQ‐Discovery (Thermo Fisher scientific, Bremen, Germany) tandem with Dionex Ultimate 3000 Nano LC system (Dionex, Thermo Fisher, Sunnyvale, USA). In the LC‐MS analysis, the on trap column‐mix method was introduced as before . The 2 cm trap column and 25 cm analytical column was packed with ReproSil‐Pur C18 AQ particles (100 Å, Dr. Maisch GmbH) 5 and 3 μm, respectively.…”

Methadone’s effect on nAChRs—a link between methadone use and smoking?

“…The active peptides generated from precursors are beta-endorphin, met-and leuenkephalins, dynorphins, and nociceptin/orphanin FQ [74,75]. Nicotine administration increases endogenous opioid levels in vivo in the NAcc and striatum [76][77][78][79]. Acute nicotine injection elevates preproenkephalin mRNA levels in the rat striatum and hippocampus, whereas chronic nicotine treatment decreases levels of preproenkephalin mRNA [80].…”

Peptidomics for the discovery and characterization of neuropeptides and hormones

“…Recently, differential comparisons have been used to probe unknown mechanisms in the physiological response to environmental [51], developmental [60] or pharmacological perturbation [31, 61, 62], disease states [36, 63–65], phenotypes [39, 66], or even various sample preparation methods crucial for successful neuropeptide detection [67, 68]. It is safe to say that relative or differential MS quantitation has already become routine due to the availability of commercial reagents, sensitive analytical instrumentation, and software.…”