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Review
. 2017 Sep;19(3):247-258.
doi: 10.31887/DCNS.2017.19.3/rspanagel.

Animal models of addiction

Rainer Spanagel  1
Affiliations
Review

Animal models of addiction

Rainer Spanagel. Dialogues Clin Neurosci. 2017 Sep.

Abstract
in English, Spanish, French

In recent years, animal models in psychiatric research have been criticized for their limited translational value to the clinical situation. Failures in clinical trials have thus often been attributed to the lack of predictive power of preclinical animal models. Here, I argue that animal models of voluntary drug intake-under nonoperant and operant conditions-and addiction models based on the Diagnostic and Statistical Manual of Mental Disorders are crucial and informative tools for the identification of pathological mechanisms, target identification, and drug development. These models provide excellent face validity, and it is assumed that the neurochemical and neuroanatomical substrates involved in drug-intake behavior are similar in laboratory rodents and humans. Consequently, animal models of drug consumption and addiction provide predictive validity. This predictive power is best illustrated in alcohol research, in which three approved medications-acamprosate, naltrexone, and nalmefene-were developed by means of animal models and then successfully translated into the clinical situation.

Los modelos animales en investigación psiquiátrica han sido criticados en los últimos años por su limitado valor para ser trasladados a la situación clínica. Las fallas en los ensayos clínicos a menudo han sido atribuidas a la falta de poder predictivo de los modelos animales preclínicos. En este artículo se argumenta que los modelos animales de ingesta voluntaria de drogas—bajo condiciones operantes y no operantes—y los modelos de adicciones basados en el Manual Diagnóstico y Estadístico de los Trastornos Mentales constituyen herramientas cruciales e informativas para la identificación de mecanismos patológicos, identificación de blancos y desarrollo de fármacos. Estos modelos aportan una excelente validez aparente y se asume que los sustratos neuroquímicos y neuroanatómicos involucrados en la conducta de ingesta de drogas son similares en los roedores de laboratorio y en los humanos. En consecuencia, los modelos animales de consumo de drogas y adicciones aportan validez predictiva. Este poder predictivo está mejor ilustrado en la investigación con alcohol, en la cual tres medicamentos aprobados (acamprosate, naltrexona y nalmefene) fueron desarrollados a partir de modelos animales y luego trasladados exitosamente a las situaciones clínicas.

Ces dernières années, les modèles animaux en recherche psychiatrique ont été critiqués pour leur valeur translationnelle limitée en situation clinique. Les échecs des études cliniques ont donc souvent été attribués au manque de puissance prédictive des modèles précliniques animaux. Pour ma part j'estime que les modèles animaux de prise volontaire de substances —sous conditions opératoires et non opératoires— et les modèles d'addiction basés sur le DSM (Diagnostic and Statistical Manual of Mental Disorders) sont des outils essentiels et informatifs pour identifier les mécanismes pathologiques et les cibles thérapeutiques et pour développer les médicaments. La validité apparente de ces modèles est excellente et on considère que les substrats neuro-chimiques et neuro-anatomiques impliqués dans le comportement de prise de substance sont similaires chez les rongeurs de laboratoire et les humains. Les modèles animaux de consommation de substances et d'addiction ont donc une validité prédictive. C'est dans la recherche sur l'alcool que cette puissance prédictive s'illustre le mieux, trois médicaments autorisés (acamprosate, nal-trexone et nalméfène) ayant été développés grâce aux modèles animaux et transférés ensuite avec succès en situation clinique.

Keywords: DSM-based animal model; biomarker; cocaine and alcohol addiction; drug self-administration; face validity; predictive validity; translational neuroimaging.

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Figures

Figure 1
Figure 1. Experimental timeline for measuring incubation of drug-seeking behavior (craving) in rats. Behavioral training and testing is according to Grimm et al. Cocaine-self-administration training consists of 16 daily (day 2 to day 1 8) 6-hour sessions during which nose poking at the active hole under a fixed ratio 1 (FR1) of response is reinforced by 0.5 mg/kg/infusion of cocaine. Cocaine availability is signaled by illumination of the blue light. Each earned infusion is coupled to the presentation of two discrete cues (light and tone). During forced abstinence (30 days), rats remain in the home cage. Cue-induced reinstatement of cocaine seeking is tested at withdrawal days 1 and 30 during a 2-hour session in the operant chamber. The first hour consists of extinction of nose-poking behavior, in which active nose poking is neither rewarded nor paired with the discrete light/tone cues. The second hour comprises cue-induced reinstatement and starts with turning on the blue light and one noncontingent presentation of the light/tone cues followed by contingent presentations of the light/tone cues in the absence of cocaine delivery. CSA, cocaine self-administration; D, day; WD, withdrawal day.
Figure 2
Figure 2. Behavioral characterization of 0crit and 3crit rats in the multisymptomatic model of cocaine addiction. 3crit rats show higher responding than 0crit rats in each criteria. (A) Persistence of cocaine seeking expressed by the sum of active nose pokes during no-drug periods in a session. (B) Motivation for cocaine intake expressed as the break point during a progressive ratio session. (C) Resistance to punishment when cocaine seeking and cocaine taking are paired with a footshock. (D) 0crit and 3crit rats do not differ in number of selfadministered cocaine injections. Data are shown as mean ± SEM; ****P<0.0001 with respect to 0crit. CSA, cocaine self-administration; SEM standard error of the mean.
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