Effects of drugs of abuse on the central neuropeptide Y system

Abstract

Neuropeptide Y (NPY), which is widely expressed in the central nervous system is involved in several neuropathologies including addiction. Here we comprehensively and systematically review alterations on the central NPY system induced by several drugs. We report on the effects of psychostimulants [cocaine, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and nicotine], ethanol, and opioids on NPY protein levels and expression of different NPY receptors. Overall, expression and function of NPY and its receptors are changed under conditions of drug exposure, thus affecting several physiologic behaviors, such as feeding, stress and anxiety. Drugs of abuse differentially affect the components of the NPY system. For example methamphetamine and nicotine lead to a consistent increase in NPY mRNA and protein levels in different brain sites whereas ethanol and opioids decrease NPY mRNA and protein expression. Drug-induced alterations on the different NPY receptors show more complex regulation pattern. Manipulation of the NPY system can have opposing effects on reinforcing and addictive properties of drugs of abuse. NPY can produce pro-addictive effects (nicotine and heroin), but can also exert inhibitory effects on addictive behavior (AMPH, ethanol). Furthermore, NPY can act as a neuroprotective agent in chronically methamphetamine and MDMA-treated rodents. In conclusion, manipulation of the NPY system seems to be a potential target to counteract neural alterations, addiction-related behaviors and cognitive deficits induced by these drugs.

RNA-seq analysis of amygdala tissue reveals characteristic expression profiles in schizophrenia

“…For example, modulators of NPY or SST signaling and drugs that increase the activity of the GABAergic pathway have been reviewed as attractive therapeutic opportunities for schizophrenia. 49 , 50 , 51 …”

Targeting redox regulation to treat substance use disorder using N‐acetylcysteine

“…Degrade cell adhesion molecules necessary for cytoskeletal stability and thereby increase synaptic plasticity (Wright & Harding, 2009) Matrix metalloproteinase inhibition reduces preference for and relapse to cocaine (Brown et al, 2007) Microtubule (Chen et al, 2012) UACC-62 cells A cytoskeletal element involved in dendritic spine morphology and synaptic plasticity (Jaworski et al, 2009) Synaptic plasticity is integral to drug-induced learning and behavior (Luscher, 2013) Myosin (Moen et al, 2014) Protein purified from Dicty orf+ cells A cytoskeletal protein that interacts with actin to influence dendritic spine morphology and synaptic plasticity (Koskinen et al, 2014) Synaptic plasticity is integral to drug-induced learning and behavior (Luscher, 2013) Na + ,K + -ATPase (Petrushanko et al, 2012) Rat myocardium The Na + ,K + -ATPase pump maintains the ionic gradient required for glutamate transporters to take up glutamate and thereby terminate its action (Rose et al, 2009) Glutamate is involved in addiction-related learning mechanisms (Tzschentke & Schmidt, 2003) Neuropeptide Y (Mullen et al, 2015) Human monocytic cells Neuropeptide involved in multiple processes including energy homeostasis (Medeiros Mdos & Turner, 1996) May induce pro-addictive effects in response to nicotine and heroin, and anti-addictive effects in response to amphetamine and ethanol (Goncalves et al, 2016)…”

From Synapse to Function: A Perspective on the Role of Neuroproteomics in Elucidating Mechanisms of Drug Addiction

“…Thus, both antagonists (naloxone) and partial agonists (buprenorphine) of these opiate receptors remain some of the few effective FDA-approved therapeutics for clinical use in treating drug addiction [63]. Research efforts studying the role of neuropeptides in addiction have not been limited to the opioid class, and a critical role has been established for a number of distinct neuropeptides, including (but not limited to) oxytocin [64], neuropeptide Y [65], substance P [66], and corticotropin releasing factor [67]. Notably, cocaine and amphetamine-regulated transcript (CART) represents a neuropeptide that was discovered due to its substantially enhanced expression following exposure to specific drugs of abuse [68].…”