- Browse by Subject
Browsing by Subject "Drug addiction"
Now showing 1 - 4 of 4
Results Per Page
Sort Options
Item A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction(Elsevier, 2016) Bell, Richard L.; Hauser, S.; Rodd, Z. A.; Liang, T.; Sari, Y.; McClintick, J.; Rahman, S.; Engleman, E. A.; Department of Psychiatry, IU School of MedicineThe purpose of this review is to present up-to-date pharmacological, genetic, and behavioral findings from the alcohol-preferring P rat and summarize similar past work. Behaviorally, the focus will be on how the P rat meets criteria put forth for a valid animal model of alcoholism with a highlight on its use as an animal model of polysubstance abuse, including alcohol, nicotine, and psychostimulants. Pharmacologically and genetically, the focus will be on the neurotransmitter and neuropeptide systems that have received the most attention: cholinergic, dopaminergic, GABAergic, glutamatergic, serotonergic, noradrenergic, corticotrophin releasing hormone, opioid, and neuropeptide Y. Herein, we sought to place the P rat's behavioral and neurochemical phenotypes, and to some extent its genotype, in the context of the clinical literature. After reviewing the findings thus far, this chapter discusses future directions for expanding the use of this genetic animal model of alcoholism to identify molecular targets for treating drug addiction in general.Item Methamphetamine (N-methylamphetamine)-induced renal disease: underevaluated cause of end-stage renal disease (ESRD)(BMJ, 2019-09-19) Baradhi, Krishna M.; Pathireddy, Samata; Bose, Subhasish; Aeddula, Narothama Reddy; Medicine, School of MedicineA 26-year-old Caucasian man with no medical history, except years of oral and intravenous drug abuse, presented with fatigue, shortness of breath, epistaxis and uncontrolled hypertension. He was pale with skin ecchymosis over his thighs and was anaemic, with severe renal failure and metabolic acidosis. Following initial clinical stabilisation of the patient, a renal biopsy was obtained, which showed vascular and glomerular changes consistent with thrombotic microangiopathic injury and advanced glomerulosclerosis. He was treated with antihypertensives and required haemodialysis. He admitted using ‘crystal meth’ regularly for many years, which is likely responsible for his renal failure. We present the case to illustrate methamphetamine-induced renal disease leading to end-stage renal disease and to bring awareness among practising clinicians, ancillary healthcare workers and public health professionals of this often undervalued cause of renal failure, which can be prevented.Item 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 MedicineAlcohol 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.Item The Reinforcing Properties of Drugs of Abuse are Attenuated by Naltrexone in Caenorhabditis elegans(Office of the Vice Chancellor for Research, 2016-04-08) Calhoun, Corey A.; Katner, Simon N.; Engleman, Eric A.; Neal-Beliveau, Bethany S.Drug addiction is a chronic, relapsing disease premised on compulsive drug seeking. Previous work from our lab demonstrated that the nematode Caenorhabditis elegans (C. elegans) can be used to examine the reinforcing properties of drugs of abuse. A successful model for studying the reinforcing effects of drugs in C. elegans would greatly aid efforts to discover potential therapeutic interventions for drug addiction. The present study examined preference for morphine, ethanol, cocaine, and a cannabinoid agonist (CB agonist) in C. elegans and the effect of naltrexone, an opioid antagonist, on this behavior. Six-well agar test plates were utilized to test drug preference. Each well had two circular target zones equidistant from the center; 4μl of the targeted drug or water were placed in the center of one of the two target zones within each well. Worms in one group were pre-treated with 10mM naltrexone, while controls were pre-treated with 0.97 mM HCl for 30 min prior to testing. Worms in each treatment group were then placed in the center of each well and allowed to move freely for 30 minutes-images were captured at 10 and 30 minutes. Animals treated with vehicle displayed a significant preference for the aforementioned drugs relative to controls; naltrexone pretreatment significantly ameliorated this effect. Naltrexone had no effect on food or chemoatractant preference, indicating that the effects of naltrexone on drug preference are selective and not due to disruption in general behaviors. These findings suggest that the reinforcing properties of drugs of abuse can be examined in C. elegans and this model may be useful for screening potential pharmacotherapies for drug abuse.