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Advancing Pharmacotherapy Development from Preclinical Animal Studies

  • Mark EgliEmail author
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 248)

Abstract

Animal models provide rapid, inexpensive assessments of an investigational drug’s therapeutic potential. Ideally, they support the plausibility of therapeutic efficacy and provide a rationale for further investigation. Here, I discuss how the absence of clear effective-ineffective categories for alcohol use disorder (AUD) medications and biases in the clinical and preclinical literature affect the development of predictive preclinical alcohol dependence (AD) models. Invoking the analogical argument concept from the philosophy of science field, I discuss how models of excessive alcohol drinking support the plausibility of clinical pharmacotherapy effects. Even though these models are not likely be completely discriminative, they are sensitive to clinically effective medications and have revealed dozens of novel medication targets. In that context, I discuss recent preclinical work on GLP-1 receptor agonists, phosphodiesterase inhibitors, glucocorticoid receptor antagonists, nocioceptin agonists and antagonists, and CRF1 antagonists. Clinically approved medications are available for each of these drug classes. I conclude by advocating a translational approach in which drugs are evaluated highly congruent preclinical models and human laboratory studies. Once translation is established, I suggest the burden is to develop hypothesis-based therapeutic interventions maximizing the impact of the confirmed pharmacotherapeutic effects in the context of additional variables falling outside the model.

Keywords

Alcohol use disorder Pharmacotherapy Preclinical models Translational research 

Abbreviations

AD

Alcohol dependence

ADE

Alcohol deprivation effect

AUD

Alcohol use disorder

BAC

Blood alcohol concentration

BNST

Bed nucleus of the stria terminalis

cAMP

Cyclic adenosine monophosphate

CeA

Central nucleus of the amygdala

cGMP

Cyclic guanosine monophosphate

CIE

Chronic intermittent ethanol

CPP

Conditioned place preference

GR

Glucocorticoid receptor

HDID

High drinking in the dark

HPA

Hypothalamus-pituitary-adrenal

LC

Locus coeruleus

N/OFQ

Nociceptin/orphanin-FQ

NAc

Nucleus accumbens

PFC

Prefrontal cortex

PVN

Paraventricular nucleus

RCT

Randomized controlled trials

SA

Self-administration

VTA

Ventral tegmental area

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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Division of Neuroscience and BehaviorNational Institute on Alcohol Abuse and Alcoholism, National Institutes of HealthBethesdaUSA

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