Research report
Excessive lever pressing following post-training signal attenuation in rats: A possible animal model of obsessive compulsive disorder?

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Abstract

This study aimed at developing a rat model of obsessive compulsive disorder based on the hypothesis that a deficient response feedback mechanism underlies obsessions and compulsions. Rats were trained to lever press for food, whose delivery was signaled by the presentation of a compound stimulus (light+tone). Subsequently, the classical contingency between the stimulus and food was extinguished (signal attenuation). Experiment 1 showed that this manipulation resulted in increased lever pressing during a subsequent extinction test, which was highly correlated with an increase in the number of trials on which the rat did not attempt to collect the food reward. This behavioral pattern was not evident in an extinction test not preceded by signal attenuation (Experiment 2), suggesting that the latter is a crucial factor in the development of this behavioral pattern. Excessive lever pressing was attenuated by the selective serotonin re-uptake inhibitor, fluoxetine (10 mg/kg; Experiment 3), but not by the anxiolytic drug, diazepam (2 mg/kg; Experiment 4). Based on these results we propose that post-training signal attenuation may provide a rat model of obsessive compulsive disorder.

Introduction

Obsessive compulsive disorder (OCD) is a psychiatric affliction with a lifetime prevalence of 1–3% [24], [29]. DSM-IV classifies OCD as an anxiety disorder characterized by obsessive thinking and compulsive behavior. A major characteristic of obsessions and compulsions is that they are excessive and unreasonable [3]. However, both obsessions and compulsions (e.g., doubting, checking, washing) may be viewed as an exaggeration of normal thoughts and behaviors [21], [25], [27].

Most current animal models of OCD can be divided into two classes, ethological and pharmacological. The former include naturally occurring repetitive or stereotypic behaviors, such as tail chasing, fur chewing, weaving, etc. (for review see Refs. [32], [36]); innate motor behaviors that occur during periods of conflict or stress (displacement behaviors) such as grooming, cleaning and pecking (for review see Ref. [22], [28], [36]); and natural behaviors that occur following some behavioral manipulations, such as schedule-induced polydipsia [37] and food restriction-induced hyperactivity [2]. Pharmacological models are based on drug-induced behavioral alterations which bear a similarity to some specific characteristics of the behavior of humans diagnosed with OCD, such as perseveration and indecision [39], or compulsive checking [6], [33].

It has been suggested that obsessions and compulsions result from a deficient response feedback mechanism or deficient signaling that the conditions have changed following the organism's response. As a result, the successful completion of an action does not lead to the cessation of that action, as would normally occur (e.g., [10], [14], [22], [26], for review see Refs. [19], [20]). The aim of the present study was to test, in rats, whether attenuation of an external feedback for operant behavior will lead to an excessive emission of this behavior. The procedure included four stages. In the first stage (magazine training) rats underwent classical conditioning to a compound stimulus (light+tone) and food, thus establishing the stimulus as a signal for the delivery of food. In the second stage (lever press training) rats were trained to lever press for food in a discrete-trial procedure (i.e., the levers were introduced into the operant box at the beginning of each trial and retracted from the box after the rat inserted its head into the food magazine to collect the food reward). Food delivery was signaled by the stimulus. In the third stage (signal attenuation) rats underwent extinction of the classical contingency between the stimulus and food. We hypothesized that the extinction of the stimulus–food contingency in this stage would attenuate the feedback provided by the stimulus on the effectiveness of the lever press response. At the last stage (test), rats’ lever press behavior was assessed under extinction conditions, i.e., pressing the lever resulted in the presentation of the stimulus, but no food was delivered. As in stage 2, the levers were retracted from the operant box only after the rat inserted its head into the food magazine, thus allowing the rat to make more than one lever press response per trial.

Since Experiment 1 showed that the procedure was effective in producing excessive lever pressing, and that this behavior was highly correlated with trials on which the rat did not attempt to collect a reward, three additional experiments were conducted to further establish this procedure as a rat model of OCD. Experiment 2 tested whether the same behavioral pattern was also induced by regular extinction of the lever press behavior (i.e., not preceded by the signal attenuation stage), and Experiments 3 and 4 tested whether this pattern would be selectively blocked by the serotonin re-uptake inhibitor (SSRI), fluoxetine, but not by the anxiolytic drug, diazepam, in accord with the differential efficacy of these drugs in treating OCD patients [5], [23], [40].

Section snippets

Subjects

Male Wistar rats (Tel-Aviv University Medical School, Israel), approximately 3 months old, weighing 300–420 g, were housed 4 to a cage under reversed cycle lighting (lights on 19:00–07:00 h). They were maintained on a 22 h food restriction schedule with freely available water, and weighed twice a week to ensure that their body weight was not reduced below 90%.

Apparatus

Behavioral testing was conducted in four operant chambers (Campden Instruments, UK) fitted with a food magazine and two retractable

Experiment 1: post-training signal attenuation

Of the 24 rats tested, seven needed a second training session on day 4. One of these rats did not attain the criterion of 20 completed trials and was excluded from the experiment. Thus, the final analysis included 23 rats.

From the second day of lever press training, rats rarely pressed the NRL, and on the last day of lever press training all rats attained 40 completed trials with no more than 2 un-pressed trials and no uncompleted trials.

There was an increase in lever presses on the RL in the

Discussion

The present study showed that extinction of a classical contingency between a stimulus signaling the availability of reward following a lever press response and the reward, led, in a subsequent test stage in which lever pressing resulted in the presentation of the signal only (i.e., extinction of operant behavior), to increased emission of the lever press response which was associated with an increased number of trials in which the rat did not attempt to collect a food pellet from the food

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