Sigma Receptors and Substance Use Disorders

Abstract

Thanks to advances in neuroscience, addiction is now recognized as a chronic brain disease with genetic, developmental, and cultural components. Drugs of abuse, including alcohol, are able to produce significant neuroplastic changes responsible for the profound disturbances shown by drug addicted individuals. The current lack of efficacious pharmacological treatments for substance use disorders has encouraged the search for novel and more effective pharmacotherapies. Growing evidence strongly suggests that Sigma Receptors are involved in the addictive and neurotoxic properties of abused drugs, including cocaine , methamphetamine , and alcohol. The present chapter will review the current scientific knowledge on the role of the Sigma Receptor system in the effects of drugs and alcohol, and proposes that this receptor system may represent a novel therapeutic target for the treatment of substance use disorders and associated neurotoxicity.

A behavioral and pharmacological characterization of palatable diet alternation in mice

“…Our results are in agreement with the previous observation that pretreatment with BD-1063 induced a selective, dose-dependent reduction of palatable food consumption in bingeing rats (Cottone et al, 2012). Though not yet tested in humans, Sig-1 receptor antagonism is a promising therapeutic target for compulsive eating (Cottone et al, 2012), as well as alcohol (Sabino and Cottone, 2016; Sabino et al, 2011; Sabino et al, 2009a; Sabino et al, 2009b; Valenza et al, 2016) and drug consumption (Hiranita et al, 2010; Nguyen et al, 2005; Sabino et al, 2017; Takahashi et al, 2000). …”

Neuroscience of Compulsive Eating Behavior

“…In binge eating humans, treatment with a MOR antagonist reduced consumption of palatable food (Ziauddeen et al, 2013 ), motivation for high calorie food stimuli (Cambridge et al, 2013 ), and hedonic responses toward a sweet food reward (Ziauddeen et al, 2013 ). Similarly, in animal studies, the Sig 1 R, a receptor involved in alcohol and drug reinforcement (Sabino et al, 2009 , 2017 ), was upregulated in prefrontal cortical brain regions following limited access to a palatable diet, and peripheral administration of a Sig 1 R antagonist blocked binge and compulsive-like eating (Cottone et al, 2012 ). TAAR1, a receptor expressed in the striatum and prefrontal cortices is activated by trace amines and has been shown to modulate cortical glutamate and dopaminergic transmission (Leo et al, 2014 ; Espinoza et al, 2015 ).…”

Trends in Sigma-1 Receptor Research: A 25-Year Bibliometric Analysis

“…The Sigma-1 receptor is considered a unique ligand-operated chaperone protein which regulates protein folding/degradation, ER/oxidative stress, and cell survival (Hayashi, 2015). Sigma-1 receptor ligands have long been expected to serve as drugs for the treatment of human diseases such as neurodegenerative disorders, depression, chronic pain, drug abuse, retinal disease, and cancer (Cobos et al, 2008; Katz et al, 2017; Kim and Maher, 2017; Maurice and Goguadze, 2017a,b; Merlos et al, 2017a,b; Sabino et al, 2017; Sanchez-Fernandez et al, 2017; Smith et al, 2018). Two subtypes of Sigma receptors have been identified, Sigma-1 and Sigma-2 (Hellewell et al, 1994).…”