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New Insights in Glutamate-Mediated Mechanisms Underlying Benzodiazepines Dependence and Cocaine Vulnerability

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Psychiatry and Neuroscience Update

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Abstract

It has been described that development and persistent expression of addictive behaviors occur through the usurpation of natural learning and memory mechanisms within the limbic system. The hippocampus (HP) and medial prefrontal cortex (mPFC) have been implicated in the neuropathological mechanisms of drug addiction and withdrawal. In cocaine-abstinent human addicts and rats in similar conditions, neuronal activity of the mPFC is increased in response to cocaine reexposure or drug-associated cues and HP synaptic plasticity was increased after both cocaine and diazepam (DZ) repeated exposure in rats. Nitric oxide (NO) is a diffusible neuromodulator synthesized in the brain primarily by glutamatergic receptors activation, and may play a role in initiating and maintaining behavioral effects of psychostimulants and also in modulation of neuronal excitability and synaptic plasticity in different brain structures including the HP and mPFC. In this chapter we discuss some of the molecular and functional changes within the HP and mPFC induced by repeated cocaine or DZ administration and the pharmacological and methodological strategies used to prevent or reverse DZ dependence and cocaine vulnerability, such as those that interfere with NO signaling, HP plasticity or alter environmental cues related to withdrawal symptoms experience. The mechanisms and strategies presented can be explored as possible targets for development of new therapeutic agents to treat dependence of and addiction to psychoactive drugs.

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Authors and Affiliations

  1. Faculty of Chemical Sciences, Department of Pharmacology-Institute of Experimental Pharmacology of Córdoba (IFEC), National University of Córdoba, National Council of Scientific and Technical Research (CONICET), Haya de la Torre y Medina Allende s/n, Ciudad Universitaria, 5000, Córdoba, Argentina

    Emilce Artur de la Villarmois Ph.D., Laura A. Gabach Ph.D. & Mariela F. Pérez Pharm.D., Ph.D.

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  1. Emilce Artur de la Villarmois Ph.D.
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  2. Laura A. Gabach Ph.D.
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  3. Mariela F. Pérez Pharm.D., Ph.D.
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Correspondence to Mariela F. Pérez Pharm.D., Ph.D. .

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Editors and Affiliations

  1. Guaymallen Mendoza, Argentina

    Pascual Ángel Gargiulo

  2. Member of the Council of the Institute of Neurobiology (Buenos Aires); Member of the Board of Certification, National Academy of Medicine (Argentina), Psychiatrist by University Complutense of Madrid and University of Buenos Aires; Former Director of National Institute of Mental Health (Argentina), Cuyo, Buenos Aires, Argentina

    Humberto Luis Mesones Arroyo

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de la Villarmois, E.A., Gabach, L.A., Pérez, M.F. (2015). New Insights in Glutamate-Mediated Mechanisms Underlying Benzodiazepines Dependence and Cocaine Vulnerability. In: Gargiulo, P., Arroyo, H. (eds) Psychiatry and Neuroscience Update. Springer, Cham. https://doi.org/10.1007/978-3-319-17103-6_13

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  • DOI: https://doi.org/10.1007/978-3-319-17103-6_13

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-17102-9

  • Online ISBN: 978-3-319-17103-6

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