<p>Studies of the role of social isolation in the pathogenesis of addictive behavioral disorders are important in relation to medical and biological problems. Of particular importance is limited social experience during ontogeny. The work reported here sought to find a connection between social isolation in ontogeny and impulsive-compulsive behavior as an indicator of the premorbid background of gaming and other forms of behavioral addictions. The mechanisms of addictive behavior in rats raised in isolation (IS) were studied by analysis of extracellular dopamine release in response to stimulation of the positive reinforcing zone. Before the experiments, male rats were kept in individual cages from day 21 of life to day 90. Elements of addictive behavior were studied using a version of the Iowa Gambling Task in a three-arm maze and a method for developing compulsive overeating by intermittent consumption of high-calorie food. Compulsive behavior was investigated using a marble burying test on the background of withdrawal of a high-calorie diet. Electrodes were implanted into the ventral tegmental area (VTA) and nucleus accumbens in rats exhibiting elements of addictive behavior in a three-arm maze. These animals were then trained to self-stimulation of the VTA. Dopamine release was recorded telemetrically in freely moving rats in response to electrical stimulation of the VTA self-stimulation zone. Fast-scan cyclic voltammetry was used to identify changes in the dopamine level in the extracellular environment of the nucleus accumbens. IS animals entered the maze arm with a high probability of low reward less often and entered the arm with a low probability of a high reward more often, which is associated with the emergence of impulsive behavior. In the compulsive overeating model, IS animals showed an increase in the number of approaches to the feeder and, on withdrawal of high-calorie food, were more active in the marble burying test. In IS animals displaying elements of addictive behavior in the three-arm maze, the extracellular dopamine level in response to electrical stimulation of the VTA self-stimulation zone did not show any differences as compared with the control group of rats with addictive behavior in the maze. At the same time, IS animals showing elements of addictive behavior in the maze produced more pronounced dopamine responses to complex stimuli, i.e., the conditioned signal used during training in the maze (light) and stimulation of the VTA. Thus, rearing in conditions of IS causes an increase in dopamine release in the nucleus accumbens in response to stimulation of the positive reinforcing zone associated with elements of addictive behavior – impulsivity and compulsivity.</p>

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Social Isolation Induces Addictive Behavior and Increased Dopamine Release in the Nucleus Accumbens in Response to Stimulation of the Positive Reinforcing Zone

  • S. S. Pyurveev,
  • A. A. Lebedev,
  • V. V. Sizov,
  • E. R. Bychkov,
  • V. N. Mukhin,
  • N. D. Nadbitova,
  • A. V. Droblenkov,
  • P. D. Shabanov

摘要

Studies of the role of social isolation in the pathogenesis of addictive behavioral disorders are important in relation to medical and biological problems. Of particular importance is limited social experience during ontogeny. The work reported here sought to find a connection between social isolation in ontogeny and impulsive-compulsive behavior as an indicator of the premorbid background of gaming and other forms of behavioral addictions. The mechanisms of addictive behavior in rats raised in isolation (IS) were studied by analysis of extracellular dopamine release in response to stimulation of the positive reinforcing zone. Before the experiments, male rats were kept in individual cages from day 21 of life to day 90. Elements of addictive behavior were studied using a version of the Iowa Gambling Task in a three-arm maze and a method for developing compulsive overeating by intermittent consumption of high-calorie food. Compulsive behavior was investigated using a marble burying test on the background of withdrawal of a high-calorie diet. Electrodes were implanted into the ventral tegmental area (VTA) and nucleus accumbens in rats exhibiting elements of addictive behavior in a three-arm maze. These animals were then trained to self-stimulation of the VTA. Dopamine release was recorded telemetrically in freely moving rats in response to electrical stimulation of the VTA self-stimulation zone. Fast-scan cyclic voltammetry was used to identify changes in the dopamine level in the extracellular environment of the nucleus accumbens. IS animals entered the maze arm with a high probability of low reward less often and entered the arm with a low probability of a high reward more often, which is associated with the emergence of impulsive behavior. In the compulsive overeating model, IS animals showed an increase in the number of approaches to the feeder and, on withdrawal of high-calorie food, were more active in the marble burying test. In IS animals displaying elements of addictive behavior in the three-arm maze, the extracellular dopamine level in response to electrical stimulation of the VTA self-stimulation zone did not show any differences as compared with the control group of rats with addictive behavior in the maze. At the same time, IS animals showing elements of addictive behavior in the maze produced more pronounced dopamine responses to complex stimuli, i.e., the conditioned signal used during training in the maze (light) and stimulation of the VTA. Thus, rearing in conditions of IS causes an increase in dopamine release in the nucleus accumbens in response to stimulation of the positive reinforcing zone associated with elements of addictive behavior – impulsivity and compulsivity.