Dataset Information

Ethanol seeking by Long Evans rats is not always a goal-directed behavior.

ABSTRACT:

Background

Two parallel and interacting processes are said to underlie animal behavior, whereby learning and performance of a behavior is at first via conscious and deliberate (goal-directed) processes, but after initial acquisition, the behavior can become automatic and stimulus-elicited (habitual). With respect to instrumental behaviors, animal learning studies suggest that the duration of training and the action-outcome contingency are two factors involved in the emergence of habitual seeking of "natural" reinforcers (e.g., sweet solutions, food or sucrose pellets). To rigorously test whether behaviors reinforced by abused substances such as ethanol, in particular, similarly become habitual was the primary aim of this study.

Methodology/principal findings

Male Long Evans rats underwent extended or limited operant lever press training with 10% sucrose/10% ethanol (10S10E) reinforcement (variable interval (VI) or (VR) ratio schedule of reinforcement), or with 10% sucrose (10S) reinforcement (VI schedule only). Once training and pretesting were complete, the impact of outcome devaluation on operant behavior was evaluated after lithium chloride injections were paired with the reinforcer, or unpaired 24 hours later. After limited, but not extended instrumental training, lever pressing by groups trained under VR with 10S10E and under VI with 10S was sensitive to outcome devaluation. In contrast, responding by both the extended and limited training 10S10E VI groups was not sensitive to ethanol devaluation during the test for habitual behavior.

Conclusions/significance

Operant behavior by rats trained to self-administer an ethanol-sucrose solution showed variable sensitivity to a change in the value of ethanol, with relative insensitivity developing sooner in animals that received time-variable ethanol reinforcement during training sessions. One important implication, with respect to substance abuse in humans, is that initial learning about the relationship between instrumental actions and the opportunity to consume ethanol-containing drinks can influence the time course for the development or expression of habitual ethanol seeking behavior.

SUBMITTER: Mangieri RA

PROVIDER: S-EPMC3411727 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Ethanol seeking by Long Evans rats is not always a goal-directed behavior.

Mangieri Regina A RA Cofresí Roberto U RU Gonzales Rueben A RA

PloS one 20120803 8

<h4>Background</h4>Two parallel and interacting processes are said to underlie animal behavior, whereby learning and performance of a behavior is at first via conscious and deliberate (goal-directed) processes, but after initial acquisition, the behavior can become automatic and stimulus-elicited (habitual). With respect to instrumental behaviors, animal learning studies suggest that the duration of training and the action-outcome contingency are two factors involved in the emergence of habitual ...[more]

PMID: 22870342

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Project description:BackgroundRodent studies have demonstrated that adolescent social isolation results in many behavioral perturbations, including increases in anxiety-like behaviors. Socially isolated (SI) rats have also been shown to self-administer greater amounts ethanol (EtOH) in some, but not all, studies. Here, we tested whether juvenile social isolation increases EtOH drinking using an intermittent procedure that engenders relatively high intake in normally reared animals. We also compared the behavioral phenotype of rats reared under social isolation or group-housed conditions with adult rats housed under conditions commonly used in EtOH-drinking studies.MethodsMale Long Evans rats were procured immediately postweaning and were group housed for 1 week. Subjects were then randomly divided into 2 groups: SI rats, housed individually for 6 weeks and group-housed (GH) rats (4/cage). A third group was procured as young adults and was housed individually upon arrival for 1 week (standard housing condition). Rats were then tested in a plus-maze and novelty assay, and then, all subjects were singly housed and EtOH drinking was assessed.ResultsSI rats displayed increased anxiety-like behaviors on the plus-maze, a greater locomotor response to a novel environment, and increased EtOH intake, relative to GH rats. Age-matched standard housed (STD) rats exhibited an anxiety-like behavioral profile on the plus-maze that was similar to SI, and not GH rats, and also drank EtOH at levels comparable with SI subjects. In addition, anxiety-like behavior on the plus-maze correlated with intermittent EtOH intake in SI and GH rats.ConclusionsThese data further support the validity of the rodent juvenile social isolation model for studies directed at elucidating behavioral and neurobiological mechanisms linking anxiety and EtOH drinking. These findings further suggest that housing conditions commonly employed in rodent drinking studies may recapitulate the anxiety-like and EtOH-drinking phenotype engendered by a juvenile social isolation procedure.

Project description:Recovery from opioid use disorder (OUD) and maintenance of abstinence from opioid use is hampered by perseverant drug cravings that may persist for months after cessation of drug use. Drug cravings can intensify during the abstinence period, a phenomenon referred to as the 'incubation of craving' that has been well-described in preclinical studies. We previously reported that animals that self-administered heroin at a dosage of 0.075 mg/kg/infusion (HH) paired with discrete drug cues displayed robust incubation of heroin craving behavior after 21 days (D) of forced abstinence, an effect that was not observed with a lower dosage (0.03 mg/kg/infusion; HL). Here, we sought to elucidate molecular mechanisms underlying long-term heroin seeking behavior by profiling microRNA (miRNA) pathways in the orbitofrontal cortex (OFC), a brain region that modulates incubation of heroin seeking. miRNAs are small noncoding RNAs with long half-lives that have emerged as critical regulators of drug seeking behavior but their expression in the OFC has not been examined in any drug exposure paradigm. We employed next generation sequencing to detect OFC miRNAs differentially expressed after 21D of forced abstinence between HH and HL animals, and proteomics analysis to elucidate miRNA-dependent translational neuroadaptations. We identified 55 OFC miRNAs associated with incubation of heroin craving, including miR-485-5p, which was significantly downregulated following 21D forced abstinence in HH but not HL animals. We bidirectionally manipulated miR-485-5p in the OFC to demonstrate that miR-485-5p can regulate long-lasting heroin seeking behavior after extended forced abstinence. Proteomics analysis identified 45 proteins selectively regulated in the OFC of HH but not HL animals that underwent 21D forced abstinence, of which 7 were putative miR-485-5p target genes. Thus, the miR-485-5p pathway is dysregulated in animals with a phenotype of persistent heroin craving behavior and OFC miR-485-5p pathways may function to support long-lasting heroin seeking.

Project description:BackgroundThere are sex differences in addiction behaviors. To develop a pre-clinical animal model to investigate this, the present study examined sex differences in sucrose taking and seeking using Long-Evans rats.MethodsFive experiments were conducted using separate groups of subjects. The first two examined sucrose or saccharin preference in two-bottle home cage choice tests. Experiment three assessed sucrose intake in a binge model with sucrose available in home cage bottles. Experiments four and five utilized operant-based procedures. In experiment four rats responded for sucrose on fixed and progressive ratio (FR, PR) schedules of reinforcement over a range of concentrations of sucrose. A final component of experiment four was measuring seeking in the absence of sucrose challenged with the dopamine D1 receptor antagonist SCH23390. Experiment five assessed responding for water on FR and PR schedules of reinforcement.ResultsWhen accounting for body weight, female rats consumed more sucrose than water; but there was no sex difference in saccharin preference over a range of saccharin concentrations. When accounting for body weight, females consumed more sucrose than males in the binge model, and only females increased binge intake over 14 days of the study. Females responded at higher rates for sucrose under both FR and PR schedules of reinforcement. Females responded at higher rates in extinction (seeking); SCH23390 reduced sucrose seeking of both females and males. Females responded at higher rates for water on FR and PR schedules than males, although rates of responding were low and decreased over sessions.ConclusionsAcross bottle-choice, binge intake, and operant procedures, female Long-Evans rats consumed more sucrose and responded at higher rates for sucrose. Although females also responded more for water, the vigor of responding did not explain the consistent sex difference in sucrose taking and seeking. The sex difference in sucrose taking was also not explained by sweet preference, as there was no sex difference in saccharin preference. These data provide a pre-clinical model to further evaluate sex differences in addiction behaviors and manipulations designed to reduce them.

Dataset Information

Ethanol seeking by Long Evans rats is not always a goal-directed behavior.

Background

Methodology/principal findings

Conclusions/significance

Publications

Ethanol seeking by Long Evans rats is not always a goal-directed behavior.

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