Oral ethanol self-administration in inbred Roman high- and low-avoidance rats: Gradual versus abrupt ethanol presentation

doi:10.1016/j.physbeh.2012.07.002

Physiology & Behavior

Volume 108, 25 December 2012, Pages 1-5

https://doi.org/10.1016/j.physbeh.2012.07.002 Get rights and content

Abstract

Outbred Roman high-avoidance rats are known to consume more ethanol than inbred Roman low-avoidance rats. To determine whether ethanol consumption in inbred strains could be modulated by experiential factors, preference for a target 10% ethanol concentration was tested after either the gradual introduction of ethanol in increasing concentrations or the abrupt introduction of the target concentration. Whereas high-avoidance rats consumed more ethanol at lower concentrations, consumption and preference for ethanol over water were not differential across strains and administration procedure (gradual vs. abrupt). At the 4% concentration, ethanol was preferred over water by Roman high-avoidance rats, but water was preferred over ethanol by Roman low-avoidance rats. Ethanol consumption and preference for a 10% concentration appear to be immune to modification by either the gradual or abrupt ethanol presentation.

Highlights

► Genetics and experiential factors affect ethanol consumption. ► Rats selected for high avoidance performance consume more ethanol than low-avoidance rats. ► At low ethanol concentrations, high-avoidance rats prefer ethanol over water. ► At low ethanol concentrations, low-avoidance rats prefer water over ethanol.

Section snippets

Subjects

The subjects were 32 male rats (16 RHA-I and 16 RLA-I) obtained from Universidad Autónoma de Barcelona, Spain (AF-T). Rats were 4 months old and weighed an average of 400 g at the start of the experiment. Animals were housed individually with free access to food and water throughout the experiment, in a room kept at 22–23 °C, and subjected to a 12:12 h light cycle (lights on at 08:00 h).

Apparatus

Access to ethanol was provided in the home cage, in 24-h cycles. Home cages were 32 × 15 × 30 cm (L × H × W), made of

Weight

Average weights for the entire experiment were 391.7, 392.4, 397.0, and 398.7 g for groups RHA-I/G, RLA-I/G, RHA-I/A, and RLA-I/A, respectively. Weights were averaged in blocks of 2 days (Blocks 1–2 correspond to pretraining, Blocks 3–6 to testing 2–8% ethanol, and Blocks 7–9 to testing 10% ethanol), and subjected to a Strain (RHA-I, RLA-I) × Group (G, A) × Block (1–9) analysis of variance, with the latter as a repeated-measure factor. There was a significant increase in weight across blocks, F(8,

Discussion

The main goal of this experiment was to determine which of two procedures for introducing a target 10% concentration of ethanol, gradual or abrupt exposure, would maximize strain differences among rats derived from artificial selection for efficiency in active avoidance learning—the Roman high-avoidance and Roman low-avoidance inbred strains (RHA-I and RLA-I, respectively). Extensive previous research revealed that the high-avoidance rats tend to score low in a variety of anxiety tests, whereas

Acknowledgments

This research was supported by Junta de Andalucía (Grant HUM-642), Ministerio de Ciencia e Innovación (Grants PSI2010-15787 and PSI2009-10532), and Fundació la MARATÓ TV3 (Grant 092630/31).

References (37)

R. Spanagel
Alcohol addiction research: from animal models to clinics
Best Pract Res Clin Gastroenterol
(2003)
M.C. Ritz et al.
Ethanol self-administration in ALKO rats: I. Effects of selection and concentration
Alcohol
(1989)
C.M.G. Aragón et al.
A correlation between voluntary ethanol consumption and brain catalase activity in the rat
Alcohol
(1985)
M.F. Lankford et al.
Drinking of high concentrations of ethanol versus palatable fluids in alcohol-preferring (P) rats: valid animal model of alcoholism
Alcohol
(1991)
G.E. Rockman et al.
Effects of restraint stress on voluntary ethanol intake and ulcer proliferation in rats
Pharmacol Biochem Behav
(1986)
P. Päivärinta et al.
Voluntary etanol drinking increases locomotor activity in alcohol‐preferring AA rats
Pharmacol Biochem Behav
(1993)
B.A. Ellenbroek et al.
Individual differences in drug dependence in rats: the role of genetic factors and life events
Eur J Pharmacol
(2005)
A. Fernández-Teruel et al.
Enduring effects of environmental enrichment on novelty seeking, saccharin and ethanol intake in two rat lines (RHA/Verh and RLA/Verh) differing in incentive-seeking behavior
Pharmacol Biochem Behav
(2002)
W. Pisula
The Roman high- and low-avoidance rats respond differently to novelty in a familiarized environment
Behav Processes
(2003)
O. Giorgi et al.
Differential activation of dopamine release in the nucleus accumbens core and shell after acute or repeated amphetamine injections: a comparative study in the Roman high- and low-avoidance rat lines
Neuroscience
(2005)

L. Giménez-Llort et al.

Two distinctive apomorphine-induced phenotypes in the Roman high- and low-avoidance rats

Physiol Behav

(2005)

D. Lecca et al.

A differential activation of dopamine output in the shell and core of the nucleus accumbens is associated with the motor responses to addictive drugs: a brain dialysis study in Roman high- and low-avoidance rats

Neuropharmacology

(2004)

O. Giorgi et al.

The psychogenetically selected Roman high- and low-avoidance rat lines: a model to study the individual vulnerability to drug addiction

Neurosci Biobehav Rev

(2007)

G.V. Kamenetzky et al.

Modelos animales para el estudio del alcoholismo

Ter Psicol

(2004)

R. Spanagel

Recent animal models of alcoholism

Alcohol Res Health

(2000)

T.-K. Li et al.

Progress toward a voluntary oral consumption model of alcoholism

Drug Alcohol Depend

(1979)

H. Samson

Initiation of ethanol reinforcement using a sucrose-substitution procedure in food- and water-sated rats

Alcohol Clin Exp Res

(1986)

J.C. Crabbe et al.

Genetic animal models of alcohol and drug abuse

Science

(1994)

Cited by (25)

Frustrative nonreward and emotional self-medication:Factors modulating alcohol consumption following reward downshift in rats
2022, Physiology and Behavior
Life experience involving unexpected incentive loss (e.g., loss of job or a significant other) may result in negative emotional reactions (frustration) and promote alcohol drinking. Similarly, animals exposed to a frustrative 32-to-4% sucrose downshift increase their preference for alcohol (2%) vs. water. This result was interpreted as reflecting emotional self-medication—the consumption of substances that reduce negative emotions. We conducted three experiments examining parametric manipulations of the animal model: (1) effects of a severe reward downshift (32-to-4% sucrose) on consumption of various alcohol concentrations (Experiment 1); (2) effects of different magnitudes of reward downshifts on consumption of 32% alcohol (Experiment 2); and (3) effects of partial reinforcement (an intervention that increases resistance to frustration) on 2% alcohol intake induced by a 32-to-4% sucrose downshift (Experiment 3). The results show that (1) a 32-to-4% sucrose downshift leads to an increase in alcohol intake over a wide range of alcohol concentrations; (2) the greater the reward downshift, the higher the relative increase in alcohol consumption; and (3) a treatment that increases resistance to frustration (partial reinforcement) also attenuates alcohol consumption after a sucrose downshift. These data are discussed in relation to the role of frustrative nonreward in alcohol consumption.
Neurobehavioral and neurodevelopmental profiles of a heuristic genetic model of differential schizophrenia- and addiction-relevant features: The RHA vs. RLA rats
2021, Neuroscience and Biobehavioral Reviews
The Roman High- (RHA) and Low-(RLA) avoidance rat lines/strains were generated through bidirectional selective breeding for rapid (RHA) vs. extremely poor (RLA) two-way active avoidance acquisition. Compared with RLAs and other rat strains/stocks, RHAs are characterized by increased impulsivity, deficits in social behavior, novelty-induced hyper-locomotion, impaired attentional/cognitive abilities, vulnerability to psychostimulant sensitization and drug addiction. RHA rats also exhibit decreased function of the prefrontal cortex (PFC) and hippocampus, increased functional activity of the mesolimbic dopamine system and a dramatic deficit of central metabotropic glutamate-2 (mGlu2) receptors (due to a stop codon mutation at cysteine 407 in Grm2 -cys407*-), along with increased density of 5-HT2A receptors in the PFC, alterations of several synaptic markers and increased density of pyramidal “thin” (immature) dendrític spines in the PFC. These characteristics suggest an immature brain of RHA rats, and are reminiscent of schizophrenia features like hypofrontality and disruption of the excitation/inhibition cortical balance. RHA rats represent a promising heuristic model of neurodevelopmental schizophrenia-relevant features and comorbidity with drug addiction vulnerability.
Reinforcing properties of alcohol in rats: Progressive ratio licking performance reinforced with 66% alcohol
2021, Physiology and Behavior
Rodents are generally reluctant to consume high concentrations of alcohol. However, few experiments have reported the behavior of rats when they are given access to high alcohol concentrations. Four experiments with food-deprived Wistar rats were designed to determine whether 66% alcohol could be used as a positive reinforcer for operant responses. In Experiment 1, animals learned to lick an empty sipper to gain access to 66% alcohol in a second tube; licking extinguished after it if provided a only access to water (operant licking task, OL). Experiment 2 used the OL task combined with a progressive ratio (PR) schedule in a within-subject design with the order of alcohol concentrations counterbalanced across subjects. The breakpoint (the last completed ratio in the PR schedule) was higher for 10% and 66% alcohol concentrations than for water. In Experiment 3, animals trained in the same PR task gained access to water, 10%, or 66% alcohol in a between-subject design. Breakpoints were higher for 66% alcohol than for water, but not for 10% alcohol relative to water. Experiment 4 tested the effects of the orexin-1 receptor antagonist SB-334,867 on licking reinforced with access to 66% alcohol in the PR task. The antagonist reduced the breakpoint at 1- and 5-mg/kg doses, but not at 10 mg/kg. These results suggest that 66% alcohol can be used to reinforce operant behavior. Although the effects were modest, they were reliable. The estimated amount of alcohol consumed in the OL task suggests that these reinforcing effects were not dependent on the pharmacological effects of 66% alcohol, but could perhaps reflect a sensation-seeking effect.
Effects of partial reinforcement on autoshaping in inbred Roman high- and low-avoidance rats
2020, Physiology and Behavior
Individuals trained under partial reinforcement (PR) typically show a greater resistance to extinction than individuals exposed to continuous reinforcement (CR). This phenomenon is referred to as the PR extinction effect (PREE) and is interpreted as a consequence of uncertainty-induced frustration counterconditioning. In this study, we assessed the effects of PR and CR in acquisition and extinction in two strains of rats, the inbred Roman high- and low-avoidance (RHA and RLA, respectively) rats. These two strains mainly differ in the expression of anxiety, the RLA rats showing more anxiety-related behaviors (hence, more sensitive to frustration) than the RHA rats. At a neurobiological level, mild stress is known to elevate corticosterone in RLA rats and dopamine in RHA rats. We tested four groups of rats (RHA/CR, RHA/PR, RLA/CR, and RLA/PR) in two successive acquisition-extinction phases to try to consolidate the behavioral effects. Animals received training in a Pavlovian autoshaping procedure with retractable levers as the conditioned stimulus, food pellets as the unconditioned stimulus, and lever presses as the conditioned response. In Phase 1, we observed a PREE in lever pressing in both strains, but this effect was larger and longer lasting in RHA/PR than in RLA/PR rats. In Phase 2, reacquisition was fast and the PREE persisted in both strains, although the two PR groups no longer differed in lever pressing. The results are discussed in terms of frustration theory and of uncertainty-induced sensitization of dopaminergic neurons.
Alcohol intake in Carioca High- and Low-conditioned Freezing rats
2020, Pharmacology Biochemistry and Behavior
Evidence from clinical and epidemiological studies point towards an association between generalized anxiety disorder (GAD) and alcohol abuse. In the present study we investigated whether a similar relationship could be observed in an animal model of GAD. Specifically, we evaluated the alcohol intake of Carioca High- and Low-conditioned Freezing rats (CHF and CLF, respectively). Sex differences in alcohol drinking behavior were also studied. Male and female rats from randomized crossbreeding populations served as controls (CTL). Free- and forced-choice protocols were used to measure alcohol consumption, and quinine and saccharin were used as taste control solutions. Our results indicate that CHF rats consumed more alcohol than CLF and CTL ones in both the free-choice (6 and 10% concentrations) and the forced-choice (10% concentration) conditions. CHF female rats exhibited the highest amount of alcohol intake in the forced-choice condition. CHF females also consumed more quinine than CHF male rats. Finally, CHF rats exhibited lower saccharin consumption compared to CLF and CTL animals. Altogether, these results support the hypothesis that there is a positive relationship between anxiety and alcohol intake, and provide further evidence for the use of CHF rats as a model of GAD.
Short-term selection for high and low ethanol intake during adolescence exerts lingering effects in stress-induced ethanol drinking and yields an anxiety-prone phenotype
2020, Behavioural Brain Research
Ethanol use is widespread in adolescents, yet only some transition to problematic drinking. It is important to understand why the risk for problematic drinking varies across sub-groups of adolescents. This study reports a short-term selection program to generate Wistar rat lines (high and low adolescent ethanol drinking, ADHI and ADLO lines, respectively) that significantly differ in ethanol drinking at adolescence. The S₀ generation and filial generations 1 (S₁), S₂, and S₃ of ADHI and ADLO offspring were tested for basal or stress-induced ethanol intake at adulthood, or for shelter-seeking and risk-taking in the multivariate concentric square field test (MSCF). The study generated lines with significant differences in free-choice ethanol drinking at adolescence. The effects of the selection were observed at adulthood, beyond the stage in which the selection was conducted: S₁-ADHI but not S₁-ADLO adult male rats exhibited stress-induced drinking. These effects were associated with significant alterations in shelter-seeking and risk-taking behaviors. ADHI rats spent significantly less time in areas of the MSCF whose exploration entails risk-taking and significantly more time in dark, sheltered areas. Some of these effects were normalized by the administration of 0.5 g/kg ethanol. There were no line differences in ethanol-induced latency to lose the righting reflex or sleep time. These findings indicate that genetic risk of enhanced ethanol intake at adolescence is still present at adulthood, long after the developmental window when the selective breeding occurred. Exposure to stress at adulthood triggers the vulnerability associated with this genetic risk, an effect associated with enhanced anxiety.

View all citing articles on Scopus

View full text

Brief communicationOral ethanol self-administration in inbred Roman high- and low-avoidance rats: Gradual versus abrupt ethanol presentation

Abstract

Highlights

Section snippets

Subjects

Apparatus

Weight

Discussion

Acknowledgments

Best Pract Res Clin Gastroenterol

Alcohol

Alcohol

Alcohol

Pharmacol Biochem Behav

Pharmacol Biochem Behav

Eur J Pharmacol

Pharmacol Biochem Behav

Behav Processes

Neuroscience

Physiol Behav

Neuropharmacology

Neurosci Biobehav Rev

Modelos animales para el estudio del alcoholismo

Ter Psicol

Recent animal models of alcoholism

Alcohol Res Health

Progress toward a voluntary oral consumption model of alcoholism

Drug Alcohol Depend

Initiation of ethanol reinforcement using a sucrose-substitution procedure in food- and water-sated rats

Alcohol Clin Exp Res

Genetic animal models of alcohol and drug abuse

Science

Brief communication
Oral ethanol self-administration in inbred Roman high- and low-avoidance rats: Gradual versus abrupt ethanol presentation