Modeling Aversion Resistant Alcohol Intake in Indiana Alcohol-Preferring (P) Rats.

With the substantial social and medical burden of addiction, there is considerable interest in understanding risk factors that increase the development of addiction. A key feature of alcohol use disorder (AUD) is compulsive alcohol (EtOH) drinking, where EtOH drinking becomes “inflexible” after chronic intake, and animals, such as humans with AUD, continue drinking despite aversive consequences. Further, since there is a heritable component to AUD risk, some work has focused on genetically-selected, EtOH-preferring rodents, which could help uncover critical mechanisms driving pathological intake.

Self-Administration of Cotinine in Wistar Rats: Comparisons to Nicotine.

Nicotine is the major addictive component in tobacco. Cotinine is the major metabolite of nicotine and a weak agonist for nicotinic acetylcholine receptors (nAChRs). Nicotine supports self-administration in rodents.

Integrated Effects of Neonatal Ventral Hippocampal Lesions and Impoverished Social-Environmental Rearing on Endophenotypes of Mental Illness and Addiction Vulnerability.

A wide range of mental illnesses show high rates of addiction comorbidities regardless of their genetic, neurodevelopmental, and/or adverse-environmental etiologies. Understanding how the spectrum of mental illnesses produce addiction vulnerability will be key to discovering more effective preventions and integrated treatments for adults with addiction and dual diagnosis comorbidities. A population of 131 rats containing a spectrum of etiological mental illness models and degrees of severity was experimentally generated by crossing neonatal ventral hippocampal lesions (NVHL; n = 68) or controls (SHAM-operated; n = 63) with adolescent rearing in environmentally/socially enriched (ENR; n = 66) or impoverished (IMP; n = 65) conditions.

Polysubstance addiction vulnerability in mental illness: Concurrent alcohol and nicotine self-administration in the neurodevelopmental hippocampal lesion rat model of schizophrenia.

Multiple addictions frequently occur in patients with mental illness. However, basic research on the brain-based linkages between these comorbidities is extremely limited. Toward characterizing the first animal modeling of polysubstance use and addiction vulnerability in schizophrenia, adolescent rats with neonatal ventral hippocampal lesions (NVHLs) and controls had 19 weekdays of 1 hour/day free access to alcohol/sucrose solutions (fading from 10% sucrose to 10% alcohol/2% sucrose on day 10) during postnatal days (PD 35-60).

Toward early estimation and treatment of addiction vulnerability: radial arm maze and N-acetyl cysteine before cocaine sensitization or nicotine self-administration in neonatal ventral hippocampal lesion rats.

Rational: Prefrontal cortical (PFC)-hippocampal-striatal circuits, interconnected via glutamatergic signaling, are dysfunctional in mental illnesses that involve addiction vulnerability.

Objectives: In healthy and neurodevelopmentally altered rats, we examined how Radial Arm Maze (RAM) performance estimates addiction vulnerability, and how starting a glutamatergic modulating agent, N-acetyl cysteine (NAC) in adolescence alters adult mental illness and/or addiction phenotypes.

Methods: Rats with neonatal ventral hippocampal lesions (NVHL) vs.

Nicotine effects in adolescence and adulthood on cognition and α₄β₂-nicotinic receptors in the neonatal ventral hippocampal lesion rat model of schizophrenia.

Rational: Nicotine use in schizophrenia has traditionally been explained as "self-medication" of cognitive and/or nicotinic acetylcholinergic receptor (nAChR) abnormalities.

Objectives: We test this hypothesis in a neurodevelopmental rat model of schizophrenia that shows increased addiction behaviors including enhanced nicotine reinforcement and drug-seeking.

Methods: Nicotine transdermal patch (5 mg/kg/day vs.

Nicotine is more addictive, not more cognitively therapeutic in a neurodevelopmental model of schizophrenia produced by neonatal ventral hippocampal lesions.

Nicotine dependence is the leading cause of death in the United States. However, research on high rates of nicotine use in mental illness has primarily explained this co-morbidity as reflecting nicotine's therapeutic benefits, especially for cognitive symptoms, equating smoking with 'self-medication'. We used a leading neurodevelopmental model of mental illness in rats to prospectively test the alternative possibility that nicotine dependence pervades mental illness because nicotine is simply more addictive in mentally ill brains that involve developmental hippocampal dysfunction.

Ventral and dorsal striatal dopamine efflux and behavior in rats with simple vs. co-morbid histories of cocaine sensitization and neonatal ventral hippocampal lesions.

Rational: Exposing animal models of mental illness to addictive drugs provides an approach to understanding the neural etiology of dual diagnosis disorders. Previous studies have shown that neonatal ventral hippocampal lesions (NVHL) in rats produce features of both schizophrenia and addiction vulnerability.

Objective: This study investigated ventral and dorsal striatal dopamine (DA) efflux in NVHL rats combined with behavioral sensitization to cocaine.

Cortical-striatal integration of cocaine history and prefrontal dysfunction in animal modeling of dual diagnosis.

Background: High rates of substance disorders in schizophrenia and other mental illnesses may reflect biological vulnerabilities to the addiction process. Interactions between addictive drug effects and mental illness involving circuits that generate motivated behavior may underpin this vulnerability.

Methods: We examined separate and combined effects of neonatal ventral hippocampal lesions (NVHLs)-a neurodevelopmental model of schizophrenia (vs.