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

Abstract

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.

Alcohol and Pain: A Translational Review of Preclinical and Clinical Findings to Inform Future Treatment Strategies

“…Chronic intermittent alcohol vapor exposure is typically experimenter‐controlled, and alcohol consumption can be assessed under operant self‐administration conditions during withdrawal. However, de Guglielmo et al () recently developed a model in which male Wistar rats voluntarily self‐administer alcohol vapor. The rats were allowed to nose poke for access to alcohol vapor in 8‐hour sessions that were conducted every other day.…”

Inhibition of Glyoxalase 1 reduces alcohol self-administration in dependent and nondependent rats

“…Rats that are made dependent by CIE exhibit clinically relevant blood alcohol levels (BALs; 150-250 mg/100 ml), an increase in alcohol drinking when tested during early and protracted abstinence, and compulsive-like alcohol drinking (e.g., responding despite adverse consequences; Kimbrough et al, 2017b;Leao et al, 2015;O'Dell et al, 2004;Roberts et al, 1996;Schulteis et al, 1995;Vendruscolo et al, 2012). Alcohol dependence that is induced by alcohol vapor results in withdrawal symptoms during both acute withdrawal and protracted abstinence (de Guglielmo et al, 2017;Kallupi et al, 2014;Macey et al, 1996;Vendruscolo and Roberts, 2014), anxiety-like behavior (Valdez et al, 2002), irritabilitylike behavior (Kimbrough et al, 2017a), and the development of mechanical hyperalgesia (Edwards et al, 2012). We hypothesized that if GLO1 is a relevant target for the treatment of AUD, then pBBG treatment will reduce alcohol self-administration in both dependent and nondependent rats.…”

An enzymatic approach reverses nicotine dependence, decreases compulsive-like intake, and prevents relapse

“…Mechanical sensitivity was evaluated using von Frey filaments (Stoelting) that ranged from 3.63 to 125.89 g as previously reported ( 37 ). The choice of the standard von Frey test instead of the electronic von Frey test or Hargreaves test was based on the ease with which comparisons can be made with our previous studies ( 8 , 38 , 39 ). Briefly, the series of von Frey filaments was applied from below the wire mesh to the central region of the plantar surface of the left and right hindpaws in ascending order, beginning with the lowest filament (3.63 g) after 10 min of habituation to the testing environment.…”