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Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models.
Chestnykh, Daria; Graßl, Fabian; Pfeifer, Canice; Dülk, Jonas; Ebner, Chiara; Walters, Mona; von Hörsten, Stephan; Kornhuber, Johannes; Kalinichenko, Liubov S; Heinrich, Markus; Müller, Christian P.
Afiliación
  • Chestnykh D; Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany.
  • Graßl F; Department of Chemistry and Pharmacy, Friedrich-Alexander-University of Erlangen-Nuremberg, Nikolaus-Fiebiger-Str. 10, 91058, Erlangen, Germany.
  • Pfeifer C; Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany.
  • Dülk J; Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany.
  • Ebner C; Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany.
  • Walters M; Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany.
  • von Hörsten S; Department of Experimental Therapy, Preclinical Experimental Center, Friedrich-Alexander-University of Erlangen-Nuremberg, Palmsanlage 5, 91054, Erlangen, Germany.
  • Kornhuber J; Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany.
  • Kalinichenko LS; Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany.
  • Heinrich M; Department of Chemistry and Pharmacy, Friedrich-Alexander-University of Erlangen-Nuremberg, Nikolaus-Fiebiger-Str. 10, 91058, Erlangen, Germany.
  • Müller CP; Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6, 91054, Erlangen, Germany. Christian.Mueller@uk-erlangen.de.
Psychopharmacology (Berl) ; 240(4): 1011-1031, 2023 Apr.
Article en En | MEDLINE | ID: mdl-36854793
RATIONALE: The dopamine D4 receptors (DRD4) play a key role in numerous brain functions and are involved in the pathogenesis of various psychiatric disorders. DRD4 ligands have been shown to moderate anxiety, reward and depression-like behaviours, and cognitive impairments. Despite a series of promising but ambiguous findings, the therapeutic advantages of DRD4 stimulation remain elusive. OBJECTIVES: The investigation focused on the behavioural effects of the recently developed DRD4 agonist, APH199, to evaluate its impact on anxiety, anhedonia, behavioural despair, establishment and retrieval of alcohol reinforcement, and amphetamine (AMPH)-induced symptoms. METHODS: Male C57BL/6 J mice and Sprague-Dawley rats were examined in five independent experiments. We assessed APH199 (0.1-5 mg/kg, i.p.) effects on a broad range of behavioural parameters in the open field (OF) test, conditioned place preference test (CPP), elevated plus maze (EPM), light-dark box (LDB), novelty suppressed feeding (NSF), forced swim test (FST), sucrose preference test (SPT), AMPH-induced hyperlocomotion test (AIH), and prepulse inhibition (PPI) of the acoustic startle response in AMPH-sensitized rats. RESULTS: APH199 caused mild and sporadic anxiolytic and antidepressant effects in EPM and FST, but no remarkable impact on behaviour in other tests in mice. However, we found a significant increase in AMPH-induced hyperactivity, suggesting an exaggeration of the psychotic-like responses in the AMPH-sensitized rats. CONCLUSIONS: Our data challenged the hypothesis of the therapeutic benefits of DRD4 agonists, pointing out a possible aggravation of psychosis. We suggest a need for further preclinical studies to ensure the safety of antipsychotics with DRD4 stimulating properties.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Agonistas de Dopamina / Receptores de Dopamina D4 Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Psychopharmacology (Berl) Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Agonistas de Dopamina / Receptores de Dopamina D4 Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Psychopharmacology (Berl) Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania