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Sheketha R. Hauser

Bio: Sheketha R. Hauser is an academic researcher from Indiana University. The author has contributed to research in topics: Nicotine & Ventral tegmental area. The author has an hindex of 20, co-authored 48 publications receiving 976 citations. Previous affiliations of Sheketha R. Hauser include Howard University & Indiana University – Purdue University Indianapolis.


Papers
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Journal ArticleDOI
TL;DR: The roles of sex‐ and age‐of‐animal, as well as the acquisition of AUDs, ethanol‐seeking and relapse continue to be factors and behaviors needing further study, while a substantial number of neurotransmitter and neuromodulatory system targets have been assessed.

106 citations

Journal ArticleDOI
TL;DR: A role for central BDNF in depressogenic effects of alcohol and antidepressant effects of nomifensine and imipramine is supported and depression per se as manifested in WKY rats may be associated with a reduction in hippocampal BDNF.
Abstract: Strong positive correlation between depression and alcoholism is evident in epidemiological reports. However, a causal relationship for this co-morbidity has not been established. We have observed that chronic daily exposure to a relatively high dose of alcohol can induce depressive-like behavior in rats and that pretreatment with nomifensine or imipramine can block the “depressogenic” effects of alcohol. Since brain derived neurotrophic factor (BDNF) is considered to play an important role in depressive-like behaviors and its elevation, particularly in the hippocampus, appears to be critical for the action of many antidepressants, we hypothesized that: 1. WKY rats, a putative animal model of depression, will show a lower hippocampal BDNF compared to their control Wistar rats, 2. Alcohol-induced depressive like behavior will be associated with a significant decrease in hippocampal BDNF and 3. Treatments with antidepressants will normalize hippocampal BDNF. These postulates were verified by measuring hippocampal BDNF in Wistar and WKY rats at baseline, following chronic (10 day) treatment with alcohol and combination of alcohol with nomifensine or imipramine. Alcohol was administered via inhalation chamber (3 h/day) such that a blood alcohol level of approximately 150 mg% was achieved. Nomifensine (10 mg/kg) or imipramine (10 mg/kg) was administered i.p. daily immediately after alcohol exposure. BDNF was measured by standard ELISA kit. The results support a role for central BDNF in depressogenic effects of alcohol and antidepressant effects of nomifensine and imipramine. Moreover, depression per se as manifested in WKY rats may be associated with a reduction in hippocampal BDNF.

69 citations

Journal ArticleDOI
TL;DR: Findings further validate the use of WKY rats as an animal model of human depression and signify the importance of inherent genetic differences in final behavioral outcome of nicotine.
Abstract: The observed high incidence of smoking amongst depressed individuals has led to the hypothesis of 'self medication" with nicotine in some of these patients. The inbred Wistar-Kyoto (WKY) rats exhibit depressive-like characteristics as evidenced by exaggerated immobility in the forced swim test (FST). One aim of this study was to investigate whether nicotine may have an antidepressant-like effect in these animals. Moreover, because of human postmortem studies indicating a reduction of the hippocampus volume in depressed patients, it was of interest to determine whether such an anatomical anomaly may also be manifested in WKY rats and whether it would be affected by chronic nicotine treatment. Adult female WKY and their control Wistar rats were administered nicotine consecutively (0.2 mg/kg, i.p., once or twice daily for 14 days) and their activity in an open field, as well as their immobility in FST were assessed either 15 min or 18 h after the last injection. Another set of animals was treated twice daily with 0.2 mg/kg nicotine for 14 days and sacrificed on day 15 for stereological evaluation of the hippocampal volume. When tested 15 min after the last injection, once or twice daily nicotine exacerbated the immobility in the FST in WKY rats only. When tested 18 h after the last injection, only twice daily nicotine treatment resulted in less immobility in the FST in WKY rats. Open field locomotor activity was not affected by any nicotine regimen. WKY rats had significantly less hippocampal volume (approximately 20%) than Wistar rats which was not altered by nicotine. These findings further validate the use of WKY rats as an animal model of human depression and signify the importance of inherent genetic differences in final behavioral outcome of nicotine.

63 citations

Journal ArticleDOI
TL;DR: In this article, the effects of nicotine on alcohol seeking and relapse at two different time points were evaluated in adult female alcohol-prefering rats with Pavlovian spontaneous recovery (PSR) and relapse.
Abstract: Background: Alcohol is frequently co-abused with smoking. In humans, nicotine use canincrease alcohol craving and consumption. The objectives of the current study were to assess theacute effects of nicotine on alcohol seeking and relapse at 2 different time points.Methods: Adult female alcohol-preferring (P) rats were trained in 2-lever operant chambers toself-administer 15% ethanol (EtOH) (v⁄v) and water on a concurrent fixed-ratio 5–fixed-ratio 1(FR5-FR1) schedule of reinforcement in daily 1-hour sessions. Following 10 weeks of daily 1-hour sessions, rats underwent 7 extinction sessions, followed by 2 weeks in their home cages. Ratswere then returned to the operant chambers without EtOH or water being present for 4 sessions(Pavlovian Spontaneous Recovery [PSR]). Rats were then given a week in their home cage beforebeing returned to the operant chambers with access to EtOH and water (relapse). Nicotine (0,0.1, 0.3, or 1.0 mg⁄kg) was injected subcutaneously immediately or 4 hours prior to PSR orrelapse testing.Results: Injections of nicotine immediately prior to testing reduced (5 to 10 responses PSR; 50to 60 responses relapse), whereas injections of nicotine 4 hours prior to testing increased (up to150 responses for PSR; up to 400 responses for relapse with 1.0 mg⁄kg dose) responses on theEtOH lever during PSR and relapse tests.Conclusions: The results of this study demonstrate that acute effects of nicotine on EtOH-seeking and relapse behaviors may be time dependent, with the immediate effects being a result ofnicotine possibly acting as a substitute for EtOH, whereas with a delay of 4 hours, priming effectsof nicotine alterations in nicotinic receptors, and⁄or the effects of nicotine’s metabolites (i.e., coti-nine and nornicotine) may enhance the expression of EtOH-seeking and relapse behaviors.Key Words: Ethanol-Seeking, Ethanol Relapse, Pavlovian Spontaneous Recovery, Nicotine,Alcohol-Preferring Rat.

52 citations

01 Jan 2017
TL;DR: A review of animal research models that can be used to screen and/or repurpose medications for the treatment of alcohol abuse and dependence can be found in this paper, where the focus is on rats and in particular selectively bred rats.
Abstract: The purpose of this review is to present animal research models that can be used to screen and/or repurpose medications for the treatment of alcohol abuse and dependence. The focus will be on rats and in particular selectively bred rats. Brief introductions discuss various aspects of the clinical picture, which provide characteristics of individuals with alcohol use disorders (AUDs) to model in animals. Following this, multiple selectively bred rat lines will be described and evaluated in the context of animal models used to screen medications to treat AUDs. Next, common behavioral tests for drug efficacy will be discussed particularly as they relate to stages in the addiction cycle. Tables highlighting studies that have tested the effects of compounds using the respective techniques are included. Wherever possible the Tables are organized chronologically in ascending order to describe changes in the focus of research on AUDs over time. In general, high ethanol-consuming selectively bred rats have been used to test a wide range of compounds. Older studies usually followed neurobiological findings in the selected lines that supported an association with a propensity for high ethanol intake. Most of these tests evaluated the compound's effects on the maintenance of ethanol drinking. Very few compounds have been tested during ethanol-seeking and/or relapse and fewer still have assessed their effects during the acquisition of AUDs. Overall, while a substantial number of neurotransmitter and neuromodulatory system targets have been assessed; the roles of sex- and age-of-animal, as well as the acquisition of AUDs, ethanol-seeking and relapse continue to be factors and behaviors needing further study. This article is part of the Special Issue entitled "Alcoholism".

51 citations


Cited by
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Journal ArticleDOI
TL;DR: Evidence is provided for notable across-species similarities in the neural consequences of adolescent alcohol exposure, providing support for further translational efforts in this context.
Abstract: Per occasion, alcohol consumption is higher in adolescents than in adults in both humans and laboratory animals, with changes in the adolescent brain probably contributing to this elevated drinking. This Review examines the contributors to and consequences of the use of alcohol in adolescents. Human adolescents with a history of alcohol use differ neurally and cognitively from other adolescents; some of these differences predate the commencement of alcohol consumption and serve as potential risk factors for later alcohol use, whereas others emerge from its use. The consequences of alcohol use in human adolescents include alterations in attention, verbal learning, visuospatial processing and memory, along with altered development of grey and white matter volumes and disrupted white matter integrity. The functional consequences of adolescent alcohol use emerging from studies of rodent models of adolescence include decreased cognitive flexibility, behavioural inefficiencies and elevations in anxiety, disinhibition, impulsivity and risk-taking. Rodent studies have also showed that adolescent alcohol use can impair neurogenesis, induce neuroinflammation and epigenetic alterations, and lead to the persistence of adolescent-like neurobehavioural phenotypes into adulthood. Although only a limited number of studies have examined comparable measures in humans and laboratory animals, the available data provide evidence for notable across-species similarities in the neural consequences of adolescent alcohol exposure, providing support for further translational efforts in this context.

314 citations

Journal ArticleDOI
20 Dec 2017-Neuron
TL;DR: This review highlights current progress in the field of ethanol use and abuse, focusing on recent and emerging molecular, cellular, and circuit effects of the drug that impact ethanol-related behaviors.

265 citations

Journal ArticleDOI
TL;DR: The hypothesis that adolescent binge drinking leads to long-lasting changes in the adult brain that increase risks of adult psychopathology, particularly for alcohol dependence, is supported.
Abstract: Adolescence is a developmental period when physical and cognitive abilities are optimized, when social skills are consolidated, and when sexuality, adolescent behaviors, and frontal cortical functions mature to adult levels. Adolescents also have unique responses to alcohol compared with adults, being less sensitive to ethanol sedative–motor responses that most likely contribute to binge drinking and blackouts. Population studies find that an early age of drinking onset correlates with increased lifetime risks for the development of alcohol dependence, violence, and injuries. Brain synapses, myelination, and neural circuits mature in adolescence to adult levels in parallel with increased reflection on the consequence of actions and reduced impulsivity and thrill seeking. Alcohol binge drinking could alter human development, but variations in genetics, peer groups, family structure, early life experiences, and the emergence of psychopathology in humans confound studies. As adolescence is common to mammalian species, preclinical models of binge drinking provide insight into the direct impact of alcohol on adolescent development. This review relates human findings to basic science studies, particularly the preclinical studies of the Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium. These studies focus on persistent adult changes in neurobiology and behavior following adolescent intermittent ethanol (AIE), a model of underage drinking. NADIA studies and others find that AIE results in the following: increases in adult alcohol drinking, disinhibition, and social anxiety; altered adult synapses, cognition, and sleep; reduced adult neurogenesis, cholinergic, and serotonergic neurons; and increased neuroimmune gene expression and epigenetic modifiers of gene expression. Many of these effects are specific to adolescents and not found in parallel adult studies. AIE can cause a persistence of adolescent-like synaptic physiology, behavior, and sensitivity to alcohol into adulthood. Together, these findings support the hypothesis that adolescent binge drinking leads to long-lasting changes in the adult brain that increase risks of adult psychopathology, particularly for alcohol dependence.

226 citations

Journal ArticleDOI
TL;DR: The pharmacology of NIC and its receptors (nAChR) and the results of functional and structural neuroimaging studies on smoking-related states and behaviors are discussed and the epidemiological, neurobiological, and genetic aspects of smoking in several specific neuropsychiatric disorders are reviewed and the clinical relevance ofsmoking in these disease states addressed.

207 citations

Journal ArticleDOI
TL;DR: This work discusses the efficacy found with nicotine, alcohol, resveratrol, curcumin, and ketamine, and the hope that neuroprotectants research gives people suffering from neurodegeneration and depression stemming from neuroinflammation.
Abstract: Neurodegeneration and depression are two common co-morbid conditions, particularly within the aging population. Research has linked neuroinflammation as a major contributing factor to both of these diseases. The key to neuroinflammation effects on neurodegeneration and depression appears to lie within the dysregulation of the control and release of pro- and anti-inflammatory cytokines. This can come from an internal or external insult to the system, or from changes in the individual due to aging that culminate in immune dysregulation. The need to reduce neuroinflammation has led to extensive research into neuroprotectants. We discuss the efficacy found with nicotine, alcohol, resveratrol, curcumin, and ketamine. Our main focus will be on what research tells us about the connections between neuroinflammation, neurodegeneration, and depression, and the hope that neuroprotectants research gives people suffering from neurodegeneration and depression stemming from neuroinflammation. We will conclude by making suggestions for future research in this area.

187 citations