Modelos animales de adicción a las drogas

Pardo, María Pilar García; Sánchez, Concepción Roger; Ortí, José Enrique de la Rubia; Aguilar, M.A.

doi:10.20882/adicciones.862

Cited by 21 publications

(9 citation statements)

References 78 publications

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“…After 30d of withdrawal, mice were brought back into the apparatus in the absence of heroin injections and significantly differentiated between active and inactive lever ( Figure 1h and i ). Taken together this experiment shows that heroin was highly reinforcing and induced seeking behavior, a widely used model for relapse ( García Pardo et al, 2017 ; Shaham et al, 2003 ).…”

Section: Resultssupporting

confidence: 53%

Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement

Corre

Zessen

Loureiro

et al. 2018

eLife

125

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The dopamine (DA) hypothesis posits the increase of mesolimbic dopamine levels as a defining commonality of addictive drugs, initially causing reinforcement, eventually leading to compulsive consumption. While much experimental evidence from psychostimulants supports this hypothesis, it has been challenged for opioid reinforcement. Here, we monitor genetically encoded DA and calcium indicators as well as cFos in mice to reveal that heroin activates DA neurons located in the medial part of the VTA, preferentially projecting to the medial shell of the nucleus accumbens (NAc). Chemogenetic and optogenetic manipulations of VTA DA or GABA neurons establish a causal link to heroin reinforcement. Inhibition of DA neurons blocked heroin self-administration, while heroin inhibited optogenetic self-stimulation of DA neurons. Likewise, heroin occluded the self-inhibition of VTA GABA neurons. Together, these experiments support a model of disinhibition of a subset of VTA DA neurons in opioid reinforcement.

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Section: Resultssupporting

confidence: 53%

Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement

Corre

Zessen

Loureiro

et al. 2018

eLife

125

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“…Previous studies have showed that TMT and elevated platform could elevate plasma corticosterone and induce heightened aggression (Dias Soares et al, 2003;Marquez et al, 2013;Papilloud et al, 2018;Wei et al, 2016), confirming their efficacy as robust stressors. After becoming adults, both male and female rats were then tested in the morphine-induced CPP and locomotor activity tests to assess vulnerability to the rewarding and psychostimulant effect of morphine in adulthood (Garcia Pardo, Roger Sanchez, De la Rubia Orti, & Aguilar Calpe, 2017;Robinson & Berridge, 1993). We found that peripubertal non-social stressors increased morphine-induced CPP and morphine-induced hyperlocomotor activity in adult male rats but not in females.…”

mentioning

confidence: 89%

Peripubertal stress of male, but not female rats increases morphine‐induced conditioned place preference and locomotion in adulthood

Wang

Zhang

Huang

et al. 2019

Developmental Psychobiology

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Animal studies demonstrate that peripubertal social stress markedly increases the risk for subsequent substance use in adulthood. However, whether non‐social stress has a similar long‐term impact is not clear, and whether male and female animals show different sensitivity to peripubertal non‐social stress has not been examined. In the present study, we addressed these issues by introducing two non‐social stressors (elevated platform and predator odor 2,5‐Dihydro‐2,4,5‐trimethylthiazoline) to male and female Wistar rats during adolescence (postnatal days 28–30, 34, 36, 40, and 42), then tested reward‐related behaviors during adulthood, including morphine‐induced conditioned place preference (CPP, 1 mg/kg morphine or 5 mg/kg morphine) and hyperlocomotor activity (5 mg/kg morphine). We found that adult male rats, but not females who were exposed to peripubertal non‐social stressors showed enhanced morphine‐induced CPP. Moreover, morphine‐induced increase in locomotor activity was also significantly increased in adult male rats, but not in females. These results indicate that peripubertal exposure to repeated non‐social stress may enhance sensitivity to the rewarding effects of opioids in adulthood in a sex‐dependent manner, with males being even more sensitive than females in this regard.

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“…Regardless, creating better preclinical models of drug addiction is essential for elucidating the neurobiological mechanisms that contribute to addiction-related behaviors, and creating better treatment options for those afflicted with addiction. In this review article, we build on the existing literature (García Pardo et al, 2017; Lynch, 2018) and discuss the various models that exist for studying addiction-related behaviors in animals, including individual variation in addiction-related behaviors, and commonalities between drug addiction and certain behavioral addictions. We then focus on how these models are used to assess abuse potential by pharmaceutical companies.…”

Section: Introductionmentioning

confidence: 99%

Understanding Addiction Using Animal Models

Kuhn

Kalivas

Bobadilla

2019

Front. Behav. Neurosci.

108

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Drug addiction is a neuropsychiatric disorder with grave personal consequences that has an extraordinary global economic impact. Despite decades of research, the options available to treat addiction are often ineffective because our rudimentary understanding of drug-induced pathology in brain circuits and synaptic physiology inhibits the rational design of successful therapies. This understanding will arise first from animal models of addiction where experimentation at the level of circuits and molecular biology is possible. We will review the most common preclinical models of addictive behavior and discuss the advantages and disadvantages of each. This includes non-contingent models in which animals are passively exposed to rewarding substances, as well as widely used contingent models such as drug self-administration and relapse. For the latter, we elaborate on the different ways of mimicking craving and relapse, which include using acute stress, drug administration or exposure to cues and contexts previously paired with drug self-administration. We further describe paradigms where drug-taking is challenged by alternative rewards, such as appetitive foods or social interaction. In an attempt to better model the individual vulnerability to drug abuse that characterizes human addiction, the field has also established preclinical paradigms in which drug-induced behaviors are ranked by various criteria of drug use in the presence of negative consequences. Separation of more vulnerable animals according to these criteria, along with other innate predispositions including goal- or sign-tracking, sensation-seeking behavior or impulsivity, has established individual genetic susceptibilities to developing drug addiction and relapse vulnerability. We further examine current models of behavioral addictions such as gambling, a disorder included in the DSM-5, and exercise, mentioned in the DSM-5 but not included yet due to insufficient peer-reviewed evidence. Finally, after reviewing the face validity of the aforementioned models, we consider the most common standardized tests used by pharmaceutical companies to assess the addictive potential of a drug during clinical trials.

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Modelos animales de adicción a las drogas

Cited by 21 publications

References 78 publications

Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement

Dopamine neurons projecting to medial shell of the nucleus accumbens drive heroin reinforcement

Peripubertal stress of male, but not female rats increases morphine‐induced conditioned place preference and locomotion in adulthood

Understanding Addiction Using Animal Models

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