Operant ethanol self-administration in ethanol dependent mice

López, Marcelo F.; Becker, Howard C.

doi:10.1016/j.alcohol.2014.02.002

Cited by 41 publications

(23 citation statements)

References 44 publications

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“…This was noteworthy in light of prior studies that have found such increases (Chu et al . ; Lopez & Becker ). One critical factor accounting for these differences may be that, unlike the current study, subjects in studies where increased self‐administration was observed received exposure to CIE between test sessions.…”

Section: Discussionmentioning

confidence: 99%

Chronic EtOH effects on putative measures of compulsive behavior in mice

et al. 2015

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Addictions, including alcohol use disorders (AUDs), are characterized by the loss of control over drug seeking and consumption, but the neural circuits and signaling mechanisms responsible for the transition from controlled use to uncontrolled abuse remain incompletely understood. Prior studies have shown that ‘compulsive-like’ behaviors in rodents, e.g., persistent responding for ethanol (EtOH) despite punishment, are increased after chronic exposure to EtOH. The main goal of the current study was to assess the effects of chronic intermittent EtOH (CIE) exposure on multiple, putative measures of compulsive-like EtOH seeking in C57BL/6J mice. Mice were exposed to two or four weekly cycles of CIE and then, post-withdrawal, tested for progressive ratio responding for EtOH, sustained responding during signaled EtOH-unavailability and (footshock) punished-suppression of responding for EtOH. Results showed that mice exposed to CIE exhibited attenuated suppression of EtOH-seeking during punishment, as compared to air-exposed controls. By contrast, CIE exposure affected neither punished food reward-seeking behavior, nor other putative measures of compulsive-like EtOH-seeking. Ex vivo RT-PCR analysis of brain tissue found reduced sensitivity to punished EtOH-seeking after CIE exposure was accompanied by a significant increase in gene expression of the GluN1 and GluN2A subunits of the N-methyl-D-aspartate receptor (NMDAR), specifically in the medial orbitofrontal cortex (mOFC). Moreover, slice electrophysiological analysis revealed increased NMDAR-mediated currents in the mOFC after CIE exposure in test-naïve mice. Collectively, the current findings add to growing body of evidence demonstrating that chronic exposure to EtOH fosters resistance to punished EtOH-seeking in association with adaptations in cortical glutamatergic transmission.

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Section: Discussionmentioning

confidence: 99%

Chronic EtOH effects on putative measures of compulsive behavior in mice

et al. 2015

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“…However, operant testing is resource-intense with greater costs in time, materials, and technicians compared with home-cage testing. Many reviews have been written on operant procedures (June and Gilpin, 2010; Lopez and Becker, 2014; Ostroumov et al, 2015; O'Tousa and Grahame, 2014; Rodd et al, 2004b; Samson and Czachowski, 2003; Vendruscolo and Roberts, 2014; Weiss, 2011), so only the basics will be covered here. The removal of the animal from their home-cage environment, transport to a test room, and placing the animal in the operant chamber results in many opportunities for the animal to form associations between environmental stimuli and learning the reinforcement value of ethanol.…”

Section: Behavioral Models For Screening Treatment Compounds And/omentioning

confidence: 99%

“…To a great extent this is also related to the first caveat, in the sense that most of the ethanol withdrawal research has been conducted in mice. We noted some of the rat research, often using outbred rat lines, in section 4.8 and Table 8; for other work and discussion see Al’Absi (2007), Becker (2013), Burke and Miczek (2014), Greenberg and Crabbe (2016), Lopez and Becker (2014), Metten et al (2014), Phillips et al (2015), Spanagel et al (2014a), Vendruscolo and Roberts (2014), as well as Zorrilla et al (2014).…”

Section: Caveats Challenges and Conclusionmentioning

confidence: 99%

Rat animal models for screening medications to treat alcohol use disorders

et al. 2017

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The purpose of this review is to present animal research models that can be used to screen and/or repurpose medications for the treatment of alcohol abuse and dependence. The focus will be on rats and in particular selectively bred rats. Brief introductions discuss various aspects of the clinical picture, which provide characteristics of individuals with alcohol use disorders (AUDs) to model in animals. Following this, multiple selectively bred rat lines will be described and evaluated in the context of animal models used to screen medications to treat AUDs. Next, common behavioral tests for drug efficacy will be discussed particularly as they relate to stages in the addiction cycle. Tables highlighting studies that have tested the effects of compounds using the respective techniques are included. Wherever possible the Tables are organized chronologically in ascending order to describe changes in the focus of research on AUDs over time. In general, high ethanol-consuming selectively bred rats have been used to test a wide range of compounds. Older studies usually followed neurobiological findings in the selected lines that supported an association with a propensity for high ethanol intake. Most of these tests evaluated the compound's effects on the maintenance of ethanol drinking. Very few compounds have been tested during ethanol-seeking and/or relapse and fewer still have assessed their effects during the acquisition of AUDs. Overall, while a substantial number of neurotransmitter and neuromodulatory system targets have been assessed; the roles of sex- and age-of-animal, as well as the acquisition of AUDs, ethanol-seeking and relapse continue to be factors and behaviors needing further study.

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“…Although no animal model of addiction fully emulates the human condition, the existing models permit investigations of specific elements of the addiction process (Rodd et al 2004). Multiple methods have been developed to produce BALs in the 100–300 mg% range for ≥12 h per day, associated with somatic and affective withdrawal symptoms, but they use a forced alcohol liquid diet (Gilpin et al 2009; Lieber and DeCarli 1982; Overstreet et al 2004), intragastric alcohol intubation (Aujla et al 2013; Braconi et al 2010; de Guglielmo et al 2015; Sidhpura et al 2010), passive exposure to alcohol vapor (Becker and Lopez 2004; de Guglielmo et al 2016; Gilpin et al 2008; Goldstein and Pal 1971; Kallupi et al 2014; Lopez and Becker 2014; O’Dell et al 2004; Rimondini et al 2002; Roberts et al 1996; Schulteis et al 1995; Vendruscolo and Roberts 2014), or selected inbred lines of alcohol-preferring rats or mice (Bell et al 2012; Ciccocioppo et al 2006; Colombo et al 2006; Crabbe et al 2014; Matson and Grahame 2013; McBride and Li 1998; Quintanilla et al 2006; Sommer et al 2006). Forced and passive administration models have limited face validity and make it difficult to unveil the neuronal networks that mediate the voluntary induction and maintenance of alcohol dependence.…”

Section: Introductionmentioning

confidence: 99%

Voluntary induction and maintenance of alcohol dependence in rats using alcohol vapor self-administration

et al. 2017

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Rationale A major issue in the addiction field is the limited number of animal models of the voluntary induction and maintenance of alcohol dependence in outbred rats. Objectives To address this issue, we developed a novel apparatus that vaporizes alcohol for 2–10 min after an active nosepoke response. Methods Male Wistar rats were allowed to self-administer alcohol vapor for 8 h/day every other day for 24 sessions (escalated) or eight sessions (non-escalated). Escalated and non-escalated rats were then tested for progressive ratio responding. Anxiety-like behavior, somatic signs of withdrawal, and hyperalgesia were assessed during acute withdrawal. Results The results showed that rats exhibited excellent discrimination between the active and inactive operanda (>85%), and the escalated rats quickly increased their blood alcohol levels from ~50 to >200 mg% in ~6 weeks. Compared with non-escalated rats, escalated rats exhibited severe addiction-like behavior, including somatic signs of withdrawal, anxiety-like behavior, hyperalgesia, and higher responding on a progressive ratio schedule of reinforcement. Conclusions These results demonstrate that outbred rats will voluntarily self-administer alcohol vapor to the point of dependence without the use of forced alcohol administration, sweeteners, food/water restriction, operant pretraining, or behavioral/genetic selection. This novel animal model may be particularly useful for medication development to help unveil the neuronal circuitry that underlies the voluntary induction of alcohol addiction and identify novel molecular targets that are specifically recruited after the voluntary induction and maintenance of alcohol dependence.

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Operant ethanol self-administration in ethanol dependent mice

Cited by 41 publications

References 44 publications

Chronic EtOH effects on putative measures of compulsive behavior in mice

Chronic EtOH effects on putative measures of compulsive behavior in mice

Rat animal models for screening medications to treat alcohol use disorders

Voluntary induction and maintenance of alcohol dependence in rats using alcohol vapor self-administration

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