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The Effects of Agonists of Ionotropic GABAA and Metabotropic GABAB Receptors on Learning

  • Evgeniya A. Zyablitseva (a1), Nikolay S. Kositsyn (a1) and Galina I. Shul'gina (a1)
Abstract

The research described here investigates the role played by inhibitory processes in the discriminations made by the nervous system of humans and animals between familiar and unfamiliar and significant and nonsignificant events. This research compared the effects of two inhibitory mediators of gamma-aminobutyric acid (GABA): 1) phenibut, a nonselective agonist of ionotropic GABAA and metabotropic GABAB receptors and 2) gaboxadol a selective agonist of ionotropic GABAA receptors on the process of developing active defensive and inhibitory conditioned reflexes in alert non-immobilized rabbits. It was found that phenibut, but not gaboxadol, accelerates the development of defensive reflexes at an early stage of conditioning. Both phenibut and gaboxadol facilitate the development of conditioned inhibition, but the effect of gaboxadol occurs at later stages of conditioning and is less stable than that of phenibut. The earlier and more stable effects of phenibut, as compared to gaboxadol, on storage in memory of the inhibitory significance of a stimulus may occur because GABAB receptors play the dominant role in the development of internal inhibition during an early stage of conditioning. On the other hand this may occur because the participation of both GABAA and GABAB receptors are essential to the process. We discuss the polyfunctionality of GABA receptors as a function of their structure and the positions of the relevant neurons in the brain as this factor can affect regulation of various types of psychological processes.

Este trabajo investiga el papel de los procesos inhibitorios en la discriminación realizada por el sistema nervioso de los humanos y los animales entre sucesos familiares y no familiares y significativos y no significativos. Se comparó los efectos de dos mediadores inhibitorios del ácido gamma-aminobutírico (GABA): 1) Phenibut, un agonista no selectivo de los receptores del GABAA ionotrópico y del GABAB metabotrópico y 2) gaboxadol, un agonista selectivo de los receptores del GABAA ionotrópico, sobre el desarrollo de reflejos condicionados de defensa activa e inhibitorios en conejos en alerta y no inmovilizados. Se encontró que el phenibut, pero no el gaboxadol, acelera el desarrollo de reflejos defensivos en una etapa temprana del condicionamiento. Tanto el phenibut como el Gaboxadol facilitaron el desarrollo de la inhibición condicionada, pero el efecto del gaboxadol ocurre en etapas tardías del condicionamiento y es menos estable que el del phenibut. Los efectos más estables y más tempranos del phenibut, en comparación con el gaboxadol, sobre el almacenaje en la memoria de la significación inhibitoria de un estímulo pueden deberse a que los receptores del GABAB tienen el papel dominante en el dearrollo de la inhibición interna durante la fase inicial del condicionamiento. Por otro lado esto puede deberse a que la participación de los receptores tanto del GABAA como del GABAB son esenciales para el proceso. Comentamos la multifuncionalidad de los receptores del GABA como función de su estructura y de las posiciones de las neuronas relevantes en el cerebro, dado que este factor puede afectar la regulación de varios tipos de procesos psicológicos.

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Corresponding author
Correspondence concerning this article should be addressed to: Shulgina Galina I., Doctor of Biological Sciences, Leading Researcher, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117465 Moscow, Butlerova 5A. (Russia). Phone: 7 (495) 789 38 52 (w), 7 (495) 940 37 74 (h), 7 (905) 700 0502 (mob). E-mail: shulgina28@mail.ru
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