Browsing by Author "Rahman, Shafiqur"

Now showing 1 - 4 of 4
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    Effects of adolescent substance use disorders on central cholinergic function
    (Elsevier, 2021) Hauser, S.R.; Rodd, Z.A.; Deehan, G.A.; Liang, T.; Rahman, Shafiqur; Bell, Richard L.; Psychiatry, School of Medicine
    Adolescence is a transitional period between childhood and adulthood, in which the individual undergoes significant cognitive, behavioral, physical, emotional, and social developmental changes. During this period, adolescents engage in experimentation and risky behaviors such as licit and illicit drug use. Adolescents' high vulnerability to abuse drugs and natural reinforcers leads to greater risk for developing substance use disorders (SUDs) during adulthood. Accumulating evidence indicates that the use and abuse of licit and illicit drugs during adolescence and emerging adulthood can disrupt the cholinergic system and its processes. This review will focus on the effects of peri-adolescent nicotine and/or alcohol use, or exposure, on the cholinergic system during adulthood from preclinical and clinical studies. This review further explores potential cholinergic agents and pharmacological manipulations to counteract peri-adolescent nicotine and/or alcohol abuse.
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    Ethanol-Associated Changes in Glutamate Reward Neurocircuitry: A Minireview of Clinical and Preclinical Genetic Findings
    (Elsevier, 2016) Bell, Richard L.; Hauser, Sheketha R.; McClintick, Jeanette; Rahman, Shafiqur; Edenberg, Howard J.; Szumlinski, Karen K.; McBride, William J.; Department of Psychiatry, IU School of Medicine
    Herein, we have reviewed the role of glutamate, the major excitatory neurotransmitter in the brain, in a number of neurochemical, -physiological, and -behavioral processes mediating the development of alcohol dependence. The findings discussed include results from both preclinical as well as neuroimaging and postmortem clinical studies. Expression levels for a number of glutamate-associated genes and/or proteins are modulated by alcohol abuse and dependence. These changes in expression include metabotropic receptors and ionotropic receptor subunits as well as different glutamate transporters. Moreover, these changes in gene expression parallel the pharmacologic manipulation of these same receptors and transporters. Some of these gene expression changes may have predated alcohol abuse and dependence because a number of glutamate-associated polymorphisms are related to a genetic predisposition to develop alcohol dependence. Other glutamate-associated polymorphisms are linked to age at the onset of alcohol-dependence and initial level of response/sensitivity to alcohol. Finally, findings of innate and/or ethanol-induced glutamate-associated gene expression differences/changes observed in a genetic animal model of alcoholism, the P rat, are summarized. Overall, the existing literature indicates that changes in glutamate receptors, transporters, enzymes, and scaffolding proteins are crucial for the development of alcohol dependence and there is a substantial genetic component to these effects. This indicates that continued research into the genetic underpinnings of these glutamate-associated effects will provide important novel molecular targets for treating alcohol abuse and dependence.
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    Nicotinic receptor modulation to treat alcohol and drug dependence
    (2015-01) Rahman, Shafiqur; Engleman, Eric A.; Bell, Richard L.; Department of Psychiatry, IU School of Medicine
    Alcohol and drug dependence are serious public health problems worldwide. The prevalence of alcohol and drug dependence in the United States and other parts of the world is significant. Given the limitations in the efficacy of current pharmacotherapies to treat these disorders, research in developing alternative pharmacotherapies continues. Preclinical and clinical evidence thus far has indicated that brain nicotinic acetylcholine receptors (nAChRs) are important pharmacological targets for the development of medications to treat alcohol and drug dependence. The nAChRs are a super family of ligand gated ion channels, and are expressed throughout the brain with twelve neuronal nAChR subunits (α2–α10 and β2–β4) identified. Here, we review preclinical and clinical evidence involving a number of nAChR ligands that target different nAChR subtypes in alcohol and nicotine addiction. The important ligands include cytisine, lobeline, mecamylamine, varenicline, sazetidine A and others that target α4β2* nAChR subtypes as small molecule modulators of the brain nicotinic cholinergic system are also discussed. Taken together, both preclinical and clinical data exist that support nAChR–based ligands as promising therapeutic agents for the treatment of alcohol and drug dependence.
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    Recent Advances in Nicotinic Receptor Signaling in Alcohol Abuse and Alcoholism
    (Elsevier, 2016) Rahman, Shafiqur; Engleman, Eric A.; Bell, Richard L.; Department of Psychiatry, IU School of Medicine
    Alcohol is the most commonly abused legal substance and alcoholism is a serious public health problem. It is a leading cause of preventable death in the world. The cellular and molecular mechanisms of alcohol reward and addiction are still not well understood. Emerging evidence indicates that unlike other drugs of abuse, such as nicotine, cocaine, or opioids, alcohol targets numerous channel proteins, receptor molecules, and signaling pathways in the brain. Previously, research has identified brain nicotinic acetylcholine receptors (nAChRs), a heterogeneous family of pentameric ligand-gated cation channels expressed in the mammalian brain, as critical molecular targets for alcohol abuse and dependence. Genetic variations encoding nAChR subunits have been shown to increase the vulnerability to develop alcohol dependence. Here, we review recent insights into the rewarding effects of alcohol, as they pertain to different nAChR subtypes, associated signaling molecules, and pathways that contribute to the molecular mechanisms of alcoholism and/or comorbid brain disorders. Understanding these cellular changes and molecular underpinnings may be useful for the advancement of brain nicotinic-cholinergic mechanisms, and will lead to a better translational and therapeutic outcome for alcoholism and/or comorbid conditions.