Nonhuman animal models of substance use disorders: Translational value and utility to basic science

Smith, Mark A.

doi:10.1016/j.drugalcdep.2019.107733

Cited by 40 publications

(33 citation statements)

References 193 publications

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“…The need for refined models that facilitate good translation from animal to human samples has been recently outlined in a National Institute on Drug Abuse (NIDA) Request for Information (RFI) to "examine the translational value of current animal models" (also see Smith, 2020).…”

Section: Introductionmentioning

confidence: 99%

Establishing preclinical withdrawal syndrome symptomatology following heroin self-administration in male and female rats.

Gipson

Dunn

Bull

et al. 2021

Experimental and Clinical Psychopharmacology

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Opioid use disorder (OUD) is a significant health problem, and understanding mechanisms of various aspects of OUD including drug use and withdrawal is important. Preclinical models provide an ideal opportunity to evaluate mechanisms underlying opioid withdrawal. Current models are limited by their reliance upon forced opioid administration, focus on the acute (and not protracted) syndrome, and exclusion of females. In this study, male and female rats selfadministered heroin (maintenance dose of 12.5 µg/kg/infusion) opioid withdrawal following abrupt discontinuation was measured. In Phase 1, acute withdrawal symptoms were rated in male and female rats at 0, 16, 48, and 72 hrs following the last self-administration session. Total somatic signs increased until 48 hrs (predominantly in females), and heroin intake positively correlated with total somatic signs at the 48 and 72 hr timepoints. Measures of hyperactivity and anxiety-like behavior increased by 16 and 48 hrs, respectively. In Phase 2, symptoms were assessed at baseline, acute, and protracted (168 and 312 hrs after self-administration) timepoints in a subset of male and female rats from Phase 1. The total number of somatic signs did not differ across timepoints, though females displayed significantly higher body temperature at all timepoints compared to males, indicating sex-specific protracted withdrawal symptomatology. These data provide a thorough characterization of rodent opioid withdrawal symptomatology following selfadministration and abrupt discontinuation that serve as a foundation for future studies designed to mimic the human experience, and demonstrate the importance of characterizing acute and protracted withdrawal with sex-specificity in preclinical models of opioid self-administration.

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Section: Introductionmentioning

confidence: 99%

Establishing preclinical withdrawal syndrome symptomatology following heroin self-administration in male and female rats.

Gipson

Dunn

Bull

et al. 2021

Experimental and Clinical Psychopharmacology

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“…Ethical constraints limit the ability to test effects of drugs with high abuse liability in drug-naïve human subjects but the role of different neurochemical mechanisms in drug-taking can be assessed using preclinical models that afford exquisite control and also can allow study of all aspects of addiction from initiation through to maintenance and relapse (Kuhn et al, 2019;Martin-Fardon & Weiss, 2013;Smith, 2020;Venniro et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Methylenedioxymethamphetamine (MDMA): Serotonergic and dopaminergic mechanisms related to its use and misuse

Schenk

Highgate

2021

Journal of Neurochemistry

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Methylenedioxymethamphetamine (MDMA) is an amphetamine analogue that preferentially stimulates the release of serotonin (5HT) and results in relatively small increases in synaptic dopamine (DA). The ratio of drug-stimulated increases in synaptic DA, relative to 5HT, predicts the abuse liability; drugs with higher DA:5HT ratios are more likely to be abused. Nonetheless, MDMA is a drug that is misused. Clinical and preclinical studies have suggested that repeated MDMA exposure produces neuroadaptive responses in both 5HT and DA neurotransmission that might explain the development and maintenance of MDMA self-administration in some laboratory animals and the development of a substance use disorder in some humans. In this paper, we describe the research that has demonstrated an inhibitory effect of 5HT on the acquisition of MDMA self-administration and the critical role of DA in the maintenance of MDMA self-administration in laboratory animals. We then describe the circuitry and 5HT receptors that are positioned to modulate DA activity and review the limited research on the effects of MDMA exposure on these receptor mechanisms.

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“…Numerous efforts to develop appropriate animal models, in which the cellular, neurobiological, and physiological aspects of alcohol dependence can be studied, are also ongoing (Panlilio and Goldberg, 2007). Contingent behavioral assays in nonhuman animals are considered essential to appropriately model human AUD (Smith, 2020). Most studies currently use rodents and monkeys for such experiments.…”

Section: Introductionmentioning

confidence: 99%

Contingent-behavior assay to study the neurogenetics of addiction shows zebrafish preference for alcohol is biphasic

Nathan

Kibat

Goel

et al. 2021

Preprint

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Alcohol use disorders are poorly understood, complex, multifactorial phenomena with a very large footprint within the global burden of diseases. Methods to study the development of addiction have primarily focused on contingent behaviors in rodents. Here, we report the development of an accessible, two-choice self-administration zebrafish assay (SAZA). Using this assay, we demonstrated that, while zebrafish avoid higher concentrations of alcohol, they are attracted to low concentrations. Pre-exposure to alcohol did not change this relative preference, and acute exposure to a deterrent decreased self-exposure to preferred concentration. A pigment mutant used in whole-brain imaging studies also displayed a similar relative preference profile but administrated substantially larger volumes of alcohol. The presence of a biphasic response (hormesis) in zebrafish validated a key aspect of vertebrate responses to alcohol. Our findings reveal the underappreciated usefulness of zebrafish in studying the neurogenetics of alcohol addiction and the discovery of novel alcohol deterrents.

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Nonhuman animal models of substance use disorders: Translational value and utility to basic science

Cited by 40 publications

References 193 publications

Establishing preclinical withdrawal syndrome symptomatology following heroin self-administration in male and female rats.

Establishing preclinical withdrawal syndrome symptomatology following heroin self-administration in male and female rats.

Methylenedioxymethamphetamine (MDMA): Serotonergic and dopaminergic mechanisms related to its use and misuse

Contingent-behavior assay to study the neurogenetics of addiction shows zebrafish preference for alcohol is biphasic

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