Nicholas E Goeders

• PhD
• Head of Faculty at Louisiana State University Health Sciences Center Shreveport

Background Pulmonary arterial hypertension (PAH) is a rare, chronic, progressive form of pulmonary hypertension in which increased arterial pressure causes remodeling of the arterial system and is associated with heart failure. Methamphetamine is a stimulant that has recently become a focus in PAH research, but the recent trends and demographics of...

Background Peripheral artery disease (PAD) is on the rise worldwide, ranking as the third leading cause of atherosclerosis-related morbidity; much less is known about its trends in hospitalizations among methamphetamine and cocaine users. Objectives We aim to evaluate the overall trend in the prevalence of hospital admission for PAD with or withou...

Purpose: This study aimed to identify the sexual effects of methamphetamine on female users and determine the factors that encourage continued use of this substance. Methods: This structured interview study was approved by the Institutional Review Board at Louisiana State University Health Shreveport. The research participants were female voluntee...

Introduction Recreational psychostimulants have been associated with increased sexual activity or changes in sexual function in women, but every drug in this class has not shown consistent sexual effects in scientific studies. Further, some studies in female animal models may recapitulate the effects observed in humans, while others produce conflic...

Background Methamphetamine is an emerging drug threat. The disparity in cardiomyopathy-associated hospital admissions among methamphetamine users (CAHMA) over the decade remains unknown. Objectives The purpose of this study was to determine the trends and prevalence of CAHMA by age, sex, race, and geographical region. Methods We used data from 20...

Objective This study compares the clinical and haemodynamic severity of methamphetamine-associated pulmonary arterial hypertension (MA-PAH) with idiopathic pulmonary arterial hypertension (IPAH) and connective tissue-associated pulmonary arterial hypertension (CTD-PAH). It also examines sex differences in clinical and physiological parameters among...

Introduction Vaginal dryness is a frequent complaint, especially in post-menopausal women. The physiology underlying the production of vaginal lubrication in response to arousing stimuli is established; however, no current pharmacological agents successfully target mechanisms within this physiology. Previous research from our lab has demonstrated t...

Background Based on previous studies of vaginal lubrication as well as our own previously reported interview study of women who self-reported methamphetamine (meth)–induced vaginal lubrication, in the current study we sought to determine the potential dose-response relationship leading to meth-induced vaginal lubrication. We also developed an anima...

Introduction Vaginal dryness is a frequent complaint, especially in post-menopausal women. The physiology underlying the production of vaginal lubrication in response to arousing stimuli is established; however, no current pharmacological agents successfully target mechanisms utilizing this physiology. Previous research from our lab has demonstrate...

Wastewater surveillance has proven to be a useful tool for evidence-based epidemiology in the fight against the SARS-CoV-2 virus. It is particularly useful at the population level where acquisition of individual test samples may be time or cost-prohibitive. Wastewater surveillance for SARS-CoV-2 has typically been performed at wastewater treatment...

The recent rise in illicit use of methamphetamine (METH), a highly addictive psychostimulant, is a huge health care burden due to its central and peripheral toxic effects. Mounting clinical studies have noted that METH use in humans is associated with the development of cardiomyopathy; however, preclinical studies and animal models to dissect detai...

Background and aims. - Healthcare workers (HCW) throughout the world have been exposed to economic and existential stress during the Covid-19 pandemic. The American Medical Association (AMA) has documented that increased healthcare burden correlates with increased HCW stress, burnout, and psychological burden. However, limits on personnel, time, an...

Methamphetamine (METH) is an addictive illicit drug used worldwide that causes significant damage to blood vessels resulting in cardiovascular dysfunction. Recent studies highlight increased prevalence of cardiovascular disease (CVD) and associated complications including hypertension, vasospasm, left ventricular hypertrophy, and coronary artery di...

Introduction Those suffering with vaginal dryness, whether experienced once or chronically, frequently experience painful and unpleasurable sexual experiences and diminished self-esteem as a result. Although the physiology of vaginal transudate production is long established, no pharmacological treatment other than estrogen has shown promise in att...

The role of previous life stress and trauma in addiction has been understudied and underappreciated. To date, much previous research has emphasized other aspects of the disease of addiction, including the reward-based neural circuitry. While previous research has offered tremendous value and shaped human understanding of addiction, an increased emp...

Introduction Vaginal dryness is an issue that affects millions of women, creating a situation that often leads to painful sexual experiences and diminished pleasure and self-esteem. Though the physiology of vaginal lubrication in response to sexually arousing stimuli is established, no treatment, other than topical lubricants, is available for wome...

Microinfusions of the endogenous neurohumor (endocoid), the opioid methionine-enkephalin, into the forebrain structure nucleus accumbens initiated a reinforcing stimulus in a dose-related manner. The reinforcing nature of this intracranial self-administration was evaluated with intermittent schedules of reinforcement and a two-lever discrimination...

Nonmedical use of prescription and nonprescription drugs is a worldwide epidemic, rapidly growing in magnitude with deaths because of overdose and chronic use. A vast majority of these drugs are stimulants that have various effects on the cardiovascular system including the cardiac rhythm. Drugs, like cocaine and methamphetamine, have measured effe...

Background: Methamphetamine (METH) is an addictive illicit drug used worldwide that can elicit significant damage on blood vessels resulting in increased inflammation and cardiovascular dysfunction. Recent studies highlight increased prevalence of cardiovascular disease (CVD) and associated complications including hypertension, vasospasm, left vent...

Methamphetamine-associated cardiomyopathy is the leading cause of death linked with illicit drug use. Here we show that Sigmar1 is a therapeutic target for methamphetamine-associated cardiomyopathy and defined the molecular mechanisms using autopsy samples of human hearts, and a mouse model of “binge and crash” methamphetamine administration. Sigma...

Introduction Illicit use of Methamphetamine (METH) in humans is associated with cardiac dysfunction known as METH‐induced cardiomyopathy. Specifically, the stimulant inhibits mitochondrial bioenergetics, resulting in energy deprivation, which may ultimately lead to the activation of the adaptive autophagy process. Objectives We aim to determine th...

Rationale Vaccines have been developed as a potential treatment for methamphetamine (meth) use disorder (MUD). Immunization with the meth vaccine IXT-v100 has previously been shown to elicit antibodies with high affinity for meth and thus may be an effective treatment for MUD. Objectives These studies were designed to determine the efficacy of IXT...

Recent genome-wide association studies (GWAS) have identified copy number variations (CNVs) at chromosomal locus 7q36.3 that significantly contribute to the risk of schizophrenia, with all of the microduplications occurring within a single gene: vasoactive intestinal peptide receptor 2 (VIPR2). To confirm disease causality and translate such a gene...

While the opioid epidemic has garnered significant attention, the use of methamphetamines is growing worldwide independent of wealth or region. Following overdose and accidents, the leading cause of death in methamphetamine users is cardiovascular disease, because of significant effects of methamphetamine on vasoconstriction, pulmonary hypertension...

The combination of metyrapone and oxazepam (Met-Ox) has recently shown promise as a pharmacotherapy for cocaine use disorder. Metyrapone is available clinically and is typically used to diagnose adrenal insufficiency, while oxazepam is often prescribed to treat anxiety. The combination of low doses of metyrapone and oxazepam has been shown to signi...

Introduction: Methamphetamine (METH) is one of the most commonly abused illicit drugs in the United States, exerting a range of adverse effects upon multiple organ systems. Cardiovascular complications are among the major causes of death in METH users. METH-induced cardiomyopathy is a poorly characterized disease entity as METH-induced molecular pe...

Glutamate dysregulation is known to contribute to many psychiatric disorders including schizophrenia. Aberrant cortico-striatal activity and therefore glutamate levels might be relevant to this disease characterized by reduced prepulse inhibition (PPI), however, the molecular and behavioral mechanism of the pathophysiology of schizophrenia remains...

The emergency department (ED) at Louisiana State University-Health Science Center in Shreveport (LSUHSC-S) serves an urban population with a large rural catchment area. This study focuses on demographic variables in substance abuse trends in this region based on urine drug screen (UDS) results. A database of de-identified UDSs ordered in the ED at...

Dysfunction of N-methyl-D-aspartate receptor (NMDAR) signaling in the nucleus accumbens (NAc) has been implicated in the pathophysiology of alcohol use disorders (AUD). Neurogranin (Ng), a calmodulin-binding protein, is exclusively expressed in the post-synapse, and mediates NMDAR driven synaptic plasticity by regulating the calcium-calmodulin (Ca2...

We have previously demonstrated that a combination of drugs (i.e., metyrapone and oxazepam) known to attenuate HPA-axis activity effectively decreases cocaine self-administration and cue reactivity in rats. However, we did not find changes in plasma corticosterone that matched the behavioral effects we observed, indicating that a different mechanis...

OBJECTIVE There is increasing interest in neuromodulation for addiction. Methamphetamine abuse is a global health epidemic with no proven treatment. The objective of this study was to examine the effects of intermittent nucleus accumbens shell (AcbSh) deep brain stimulation (DBS) on operant methamphetamine intake and on methamphetamine seeking when...

Background: Methamphetamine is the second most commonly used illicit drug in the world, and despite recent attempts by the Drug Enforcement Administration to combat this epidemic, methamphetamine use is still on the rise. As methamphetamine use increases so does polydrug use, particularly that involving methamphetamine and benzodiazepines. The pre...

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to in...

Drug users often combine benzodiazepines with psychostimulants, such as methamphetamine. However, very little research has been conducted on this type of polydrug use, particularly in female subjects. The present study was therefore designed to examine the effects of two benzodiazepines, alprazolam and oxazepam, on the discriminative stimulus effec...

In rodents, the behavioral and neurochemical effects resulting from the pharmacological blockade of the hypothalamo-pituitary-adrenal (HPA) axis are unclear. Metyrapone, a corticosterone synthesis inhibitor, has been demonstrated to reduce cocaine-related behaviors, especially in a low-dose combination with oxazepam, a benzodiazepine. Although this...

Previous research has demonstrated a complicated role for stress and HPA axis activation in potentiating various cocaine-related behaviors in preclinical models of drug dependence. However, the investigation of several antiglucocorticoid therapies has yielded equivocal results in reducing cocaine-related behaviors, possibly because of varying mecha...

Investigation of the role of stress in cocaine addiction has yielded an efficacious combination of metyrapone and oxazepam, hypothesized to decrease relapse to cocaine use by reducing stress-induced craving. However, recent data suggest an extra-adrenal role for metyrapone in mediating stress- and addiction-related behaviors. The interactions betwe...

Although scientists have been investigating the neurobiology of psychomotor stimulant reward for many decades, there is still no FDA-approved treatment for cocaine or methamphetamine abuse. Research in our laboratory has focused on the relationship between stress, the subsequent activation of the hypothalamic-pituitary-adrenal (HPA) axis, and psych...

Several compounds that potentiate GABA-induced inhibitory currents also decrease stress, anxiety and addiction-related behaviors. Because of the well-established connection between stress and addiction, compounds that reduce stress-induced responses might be efficacious in treating addiction. Since endogenous neurosteroids such as allopregnanolone...

Background. Research has shown that methamphetamine use is associated with higher-risk sexual behaviors and an increased likelihood of HIV & STI acquisition. While there is little research on the motivations of meth use outside of urban MSM populations, what research does exist points to sexual enhancement as a central motivating factor. This study...

Research has shown that while using meth there is a higher likelihood of engaging in sex without a condom and having sex with multiple partners, behaviors that may lead to a higher risk of acquiring HIV and other STIs. Women use meth for a variety of reasons including to lower inhibitions and to increase energy, which often leads to prolonged and h...

Background: Previous studies have found methamphetamine (meth) use to be associated with many negative health consequences, such as Hepatitis and HIV transmission, as well as social, physical, and psychological consequences. Meth is a frequent drug of use in the United States. In recent years, research focused on female methamphetamine use has incr...

Background. Methamphetamine use is commonly associated with the loss of inhibitory control and sexually compulsive behavior, often leading to sexual aggression with intimate partners. In addition, these behaviors contribute to an increased risk for the acquisition of sexually transmitted infections (STIs) and HIV, as well as psychological harms inc...

Methamphetamine (MA) is a highly addictive psychostimulant drug of abuse for which no FDA-approved treatment exists. While high on MA, both male and female MA users report engaging in risky behaviors and are more likely to be involved in violent criminal activities and to engage in domestic and sexual violence. A unique aspect of MA is that it is t...

We have previously reported that combining low doses of oxazepam and metyrapone (OX/MET) reduces intravenous cocaine self-administration without affecting stress-hormone levels. We hypothesized that the combination of OX/MET would also inhibit the reinstatement of cocaine or methamphetamine seeking induced by the presentation of a conditioned reinf...

Neuropeptide S (NPS) is a neuromodulatory peptide, acting via a G-protein-coupled receptor to regulate sleep, anxiety and behavioral arousal. Recent research has found that intracerebroventricular NPS can increase cocaine and alcohol self-administration in rodents, suggesting a key role in reward-related neurocircuitry. It is hypothesized that anta...

Despite increased education regarding its dangers, cigarette smoking remains a significant public health concern due to serious associated health consequences such as cancer and respiratory and cardiovascular diseases. Most smokers fail in their attempts to quit smoking, and current pharmacological interventions have relatively low levels of effica...

Although cocaine dependence affects an estimated 1.6 million people in the USA, there are currently no medications approved for the treatment of this disorder. Experiments performed in animal models have demonstrated that inhibitors of the stress response effectively reduce intravenous cocaine self-administration. This exploratory, double-blind, pl...

Methamphetamine (MA) increases extracellular dopamine (DA) and at chronic high doses induces toxicity as indicated by decreased expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT). Notably, rats will self-administer MA in escalating quantities producing such toxicity. However, the impact of MA at sub-toxic doses on DA regulation...

Methamphetamine (meth) is widely recognized as being associated with violence and aggression. This association is found among women and men, with rates of meth-related violence among women possibly being equal to or even exceeding rates among men. This study examined female-perpetrated violence from the phenomenological point of view of 30 women (a...

Aims: The nexus of methamphetamine (meth) use, risky sexual behavior, and intimate partner violence is not well understood. The aims of this paper are to explore women meth users' experiences of risky sexual behavior in relation to intimate partner violence, and to analyze these experiences with regard to HIV risk. Methods: Thirty women in resident...

Although our lab, as well as several others, has demonstrated a role for corticosterone in cocaine self-administration, there are no studies of the central dynamics of this hormone over the course of a behavioral session when rats are self-administering cocaine or receiving passive injections. The assay of corticosterone in microdialysates collecte...

Fluoxetine is a SSRI commonly used to treat depression. Like other SSRIs, it blocks the reuptake of serotonin, a neurotransmitter involved in mood regulation, at the neuronal synapse. Methamphetamine users experience a "high" due in part to the release of excess serotonin in the brain. Therefore, it can be assumed that some of the same neurological...

For several years, our laboratory has investigated the role for the HPA axis in cocaine reinforcement. Two classes of drugs that we have studied include corticosterone synthesis inhibitors (e.g., metyrapone) and benzodiazepine receptor agonists (e.g., oxazepam). In the experiments described in this manuscript, we tested the effects of various doses...

We have previously reported that pretreatment with benzodiazepines reduces intravenous cocaine self-administration in rats. This experiment was designed to investigate whether or not benzodiazepines would also inhibit the reinstatement of cocaine seeking induced by the presentation of a conditioned reinforcer. Adult male rats were implanted with ju...

Anecdotal and scientific evidence suggests a link between substance abuse and stress. One explanation for the high concordance between stress-related disorders and drug addiction is the self-medication hypothesis, which suggests that a dually-diagnosed person often uses the abused substance to cope with tension associated with life stressors or to...

Previous studies from our laboratory and others have indicated a role for the hypothalamo-pituitary-adrenal (HPA) axis in the extinction/reinstatement animal model of cocaine relapse This present study was designed to investigate the potential role for the HPA axis in the cue- and methamphetamine-induced reinstatement of extinguished methamphetamin...

Recent genetic and pharmacological studies have suggested that the metabotropic glutamate receptor subtype 5 (mGluR5) may represent a druggable target in identifying new therapeutics for the treatment of various central nervous system disorders including drug abuse. In particular, considerable attention in the mGluR5 field has been devoted to ident...

Previous research has indicated a role for the hypothalamo-pituitary-adrenal (HPA) axis in the acquisition of intravenous cocaine self-administration since both exposure to stressors and exogenous injections of corticosterone facilitate this behavior. The present experiment was designed to determine whether electric footshock or pretreatment with c...

This article will review data obtained from both clinical and preclinical investigations demonstrating that exposure to stress has a significant impact on drug addiction. The preclinical literature suggests that stress increases reward associated with psychomotor stimulants, possibly through a process similar to sensitization. While it is not concl...

It has been suggested that stress, via corticosterone secretion, can modulate some of the behavioural responses to cocaine. In particular, we have demonstrated that daily exposure to electric footshock stress or daily pretreatment with corticosterone shifts the ascending limb of the dose-response curve for the acquisition of cocaine self-administra...

In an elegant series of experiments, F. Leri and J. Stewart (2002) report that exposure to heroin increases subsequent reinstatement responding if the animal has access to the drug lever during the lapse and if responding on the lever results in the presentation of conditioned cues. It is interesting that exposure to only these conditioned cues in...

Conditioned cues associated with cocaine induce craving and relapse. Although the role of corticotropin releasing hormone (CRH) in stress- and cocaine-induced relapse has been reported, its involvement in cue-induced behavior has not been established. Using responding during extinction as a model of cue-induced craving, we tested the effects of a s...

Research from our laboratory has explored the role of the hypothalamo-pituitary-adrenal (HPA) axis in cocaine reinforcement. These experiments were designed to determine the involvement of the HPA axis in extinction. Male Wistar rats were trained to self-administer cocaine [0.125, 0.25, or 0.5 mg/kg/infusion (inf)] and food pellets (45 mg) under a...

The role for corticotropin-releasing hormone (CRH) receptors in the maintenance of intravenous cocaine self-administration in rats was investigated using the centrally active, small molecule CRH1 receptor antagonist CP-154,526. In these experiments, adult male Wistar rats were allowed alternating 15-min periods of access to food reinforcement and c...

1.1. The effects of chronic (i.e., 30-day), high-dose (i.e., 1.0 mg/kg/infusion) intravenous cocaine self-administration and non-contingent infusions of cocaine and saline on plasma corticosterone and hippocampal Type II glucocorticoid receptors (GR) were investigated in adult male Wistar rats implanted with indwelling jugular catheters using a sel...

Ketoconazole (Keto) is an antifungal agent that also inhibits the synthesis of adrenocorticosteroids and has been reported to act as a glucocorticoid receptor antagonist. The present experiments investigated the effects of Keto on the stressor-induced reinstatement of extinguished cocaine-seeking behavior and on the generalization of a stressor-ind...

Ketoconazole is an oral antimycotic agent approved by the FDA for the treatment of fungal disease which also blocks the synthesis of adrenocorticosteroids and functions as a glucocorticoid receptor antagonist. In these experiments, adult male Wistar rats were allowed alternating 15-min periods of access to food reinforcement and cocaine self-admini...

The effect of corticosterone on the acquisition of cocaine-seeking behavior was investigated in rats using ascending dose-response curves for intravenous cocaine self-administration. Rats pretreated daily with corticosterone (2.0 mg/kg i.p.) acquired cocaine self-administration at a lower dose compared with vehicle-treated controls. In contrast, da...

In nonlaboratory settings, social users of cocaine are sometimes able to control their drug intake so their patterns of use do not escalate to levels that would increase their risk of dependency and toxicity (Siegel 1984). This suggests that there may be factors in addition to the primary reinforcing properties of cocaine that determine why some in...

The ability of the interoceptive cues produced following exposure to restraint stress to generalize to the discriminative stimulus effects of cocaine was investigated. Rats were trained to discriminate cocaine (10 mg/kg, IP, n=10; or 20 mg/kg, IP, n=6) from saline using a two-choice, food-reinforced, drug discrimination design. Substitution for the...

Cocaine stimulates the secretion of corticosterone and ACTH, probably through a CRF-related mechanism, indicating that the drug activates the HPA axis. Indeed, cocaine has been reported to produce anxiety and to precipitate episodes of panic attack during chronic use and withdrawal in humans and to induce anxiogenic behavior in animals. Cocaine als...

There is evidence to suggest that cocaine acts centrally to enhance adrenocortical secretory activity and this effect may be associated with the reinforcing properties of this drug. Lewis (LEW) and Fischer (F344) rats are inbred strains which differ in their responses to the reinforcing effects of cocaine. Previous findings from this laboratory hav...

Tolerance and sensitization to the behavioral effects of cocaine were investigated in rats responding under a fixed-consecutive-number eight schedule of food reinforcement. The development of tolerance or sensitization was induced by delivering the drug either immediately before or after each behavioral session during chronic administration. Chroni...

The role of corticosterone in cocaine reinforcement was investigated in rats exposed to either response-contingent electric footshock, noncontingent shock or no shock prior to the initiation of testing for intravenous cocaine self-administration. Although rats from the two shock groups were consistently more sensitive to cocaine, plasma corticoster...

Previous research has suggested the potential involvement of the hypothalamic-pituitary-adrenal (HPA) axis in psychostimulant reinforcement. In particular, we have found significant correlations between electric footshock-induced increases in plasma corticosterone and the acquisition, or lack thereof, of intravenous cocaine self-administration in r...

Lewis (LEW) and Fischer 344 (F344) rats differ in responsiveness of the hypothalamo-pituitary-adrenocortical (HPA) axis as well as in their behavioral responses to drugs of abuse. The present experiments were conducted to compare hypothalamic corticotropin-releasing factor (CRF), plasma adrenocorticotropic hormone (ACTH) and plasma corticosterone (...

The experiments described below were designed to investigate whether contingent versus non-contingent electric footshock would affect the acquisition of intravenous cocaine self-administration in rats. During the first component of a multiple schedule, triads of rats were trained to respond under a discrete-trial, fixed-ratio 10 schedule of food re...

Adult male rats were trained to intracranially self-administer cocaine (50-100 pmol/100 nl infusion) into the medial prefrontal cortex and to simultaneously deliver an infusion of vehicle (100 nl of artificial cerebrospinal fluid) to a littermate control. When stable base lines of responding were obtained, each rat was implanted with an indwelling...

The specificity of benzodiazepine pretreatment on the reinforcing efficacy of cocaine was investigated using a multiple schedule of cocaine and food presentation. Cocaine was available under a fixed-ratio 4 schedule of reinforcement during 1 h of the session, while food was delivered under a discrete-trial, fixed-ratio 10 schedule during the other....

Cocaine (COC) has been described as exerting potent stimulatory effects on the hypothalamo-pituitary-adrenocortical (HPA) axis. In the present study, we investigated the acute and chronic effects of intracerebroventricular and intrahypothalamic injections of COC in rats. Twenty minutes following intracerebroventricular injection of COC (1-100 micro...