title: Cognitive enhancers versus addictive psychostimulants: The good and bad side of dopamine on prefrontal cortical circuits.
abstract: In this review we describe how highly addictive psychostimulants such as cocaine and methamphetamine actions might underlie hypoexcitabilty in frontal cortical areas observed in clinical and preclinical models of psychostimulant abuse. We discuss new mechanisms that describe how increments on synaptic dopamine release are linked to reduce calcium influx in both pre and postsynaptic compartments on medial PFC networks, therefore modulating synaptic integration and information. Sustained DA neuromodulation by addictive psychostimulants can "lock" frontal cortical networks in deficient states. On the other hand, other psychostimulants such as modafinil and methylphenidate are considered pharmacological neuroenhancement agents that are popular among healthy people seeking neuroenhancement. More clinical and preclinical research is needed to further clarify mechanisms of actions and physiological effects of cognitive enhancers which show an opposite pattern compared to chronic effect of addictive psychostimulants: they appear to increase cortical excitability. In conclusion, studies summarized here suggest that there is frontal cortex hypoactivity and deficient inhibitory control in drug-addicted individuals. Thus, additional research on physiological effects of cognitive enhancers like modafinil and methylphenidate seems necessary in order to expand current knowledge on mechanisms behind their therapeutic role in the treatment of addiction and other neuropsychiatric disorders.
authors.affiliation: Instituto de Investigaciones Farmacológicas (Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina. Electronic address: vbisagno@ffyb.uba.ar.
authors.forename: Veronica
authors.initials: V
authors.lastname: Bisagno
authors.affiliation: Instituto de Investigaciones Farmacológicas (Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Betina
authors.initials: B
authors.lastname: González
authors.affiliation: Laboratorio de Fisiología y Biología Molecular, Instituto de Fisiología, Biología Molecular y Neurociencias, Departamento de Fisiología, Biología Molecular y Celular "Prof. Dr. Héctor Maldonado" (Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Urbano
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008694:Methamphetamine / Q000494:pharmacology; D008774:Methylphenidate / Q000494:pharmacology; D000077408:Modafinil; D018697:Nootropic Agents / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D019966:Substance-Related Disorders / Q000378:metabolism / Q000503:physiopathology
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D018697:Nootropic Agents; D008774:Methylphenidate; D008694:Methamphetamine; D003042:Cocaine; D000077408:Modafinil; D004298:Dopamine
keywords: Calcium channels; Cocaine; Dopamine; Hyperpolarization-activated cation current; Methamphetamine; Methylphenidate; Modafinil; Prefrontal cortex