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Swiprosin1/EFhd2 is involved in the monoaminergic and locomotor responses of psychostimulant drugs.
Kogias, Georgios; Zheng, Fang; Kalinichenko, Liubov S; Kornhuber, Johannes; Alzheimer, Christian; Mielenz, Dirk; Müller, Christian P.
Affiliation
  • Kogias G; Department of Psychiatry and Psychotherapy, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
  • Zheng F; Institute of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
  • Kalinichenko LS; Department of Psychiatry and Psychotherapy, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
  • Kornhuber J; Department of Psychiatry and Psychotherapy, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
  • Alzheimer C; Institute of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
  • Mielenz D; Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus-Fiebiger-Center, University Clinic, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
  • Müller CP; Department of Psychiatry and Psychotherapy, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
J Neurochem ; 154(4): 424-440, 2020 08.
Article in En | MEDLINE | ID: mdl-31943210
ABSTRACT
Psychostimulants are widely abused drugs that may cause addiction in vulnerable individuals. While the reward circuitry of the brain is involved in addiction establishment, various pathways in the brain may provide protection at the molecular level that limits the acute and chronic effects of drugs. These targets may be used for strategies designed to prevent and treat addiction. Swiprosin-1/EF hand domain 2 (EFhd2) is a Ca2+ -binding cytoskeletal adaptor protein involved in sensation-seeking behaviour, anxiety and alcohol addiction. Here, we tested how EFhd2 contributes to the physiological and behavioural effects of the psychostimulant drugs methamphetamine (METH) and cocaine. An in vivo microdialysis study in EFhd2 knockout mice revealed that EFhd2 controls METH- and cocaine-induced changes in extracellular dopamine, serotonin and noradrenaline levels through different mechanisms in the nucleus accumbens and prefrontal cortex. Electrophysiological recordings in a slice preparation showed that a lack of EFhd2 increases dopaminergic neuronal activity in the ventral tegmental area and increases the sensitivity of neurons to stimulation. We report a role of EFhd2 in METH-induced locomotor activation and in the conditioned locomotor effects. No role, however, was observed in the establishment of METH- or cocaine-induced conditioned place preference. These findings may suggest that EFhd2 modulates the activity of the dopaminergic system and the neurochemical effects of METH and cocaine, which translate into a modulation of the behavioural effects of these drugs at the level of the acute and conditioned locomotor activity.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain / Calcium-Binding Proteins / Cocaine / Central Nervous System Stimulants / Locomotion / Methamphetamine Limits: Animals Language: En Journal: J Neurochem Year: 2020 Document type: Article Affiliation country: Germany

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain / Calcium-Binding Proteins / Cocaine / Central Nervous System Stimulants / Locomotion / Methamphetamine Limits: Animals Language: En Journal: J Neurochem Year: 2020 Document type: Article Affiliation country: Germany
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