Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models

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 promis...
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Autor*in:	Chestnykh, Daria [verfasserIn] Graßl, Fabian Pfeifer, Canice Dülk, Jonas Ebner, Chiara Walters, Mona von Hörsten, Stephan Kornhuber, Johannes Kalinichenko, Liubov S. Heinrich, Markus Müller, Christian P.

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	DRD4 agonist APH199 Anxiety Depression Schizophrenia Psychosis Alcohol

Anmerkung:	© The Author(s) 2023

Übergeordnetes Werk:	Enthalten in: Psychopharmacology - Berlin : Springer, 1959, 240(2023), 4 vom: 28. Feb., Seite 1011-1031
Übergeordnetes Werk:	volume:240 ; year:2023 ; number:4 ; day:28 ; month:02 ; pages:1011-1031

Links:	Volltext

DOI / URN:	10.1007/s00213-023-06347-1

Katalog-ID:	SPR049629557

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100	1		\|a Chestnykh, Daria \|e verfasserin \|4 aut
245	1	0	\|a Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models
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520			\|a 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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700	1		\|a Graßl, Fabian \|4 aut
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700	1		\|a Walters, Mona \|4 aut
700	1		\|a von Hörsten, Stephan \|4 aut
700	1		\|a Kornhuber, Johannes \|4 aut
700	1		\|a Kalinichenko, Liubov S. \|4 aut
700	1		\|a Heinrich, Markus \|4 aut
700	1		\|a Müller, Christian P. \|4 aut
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publishDate	2023
allfields	10.1007/s00213-023-06347-1 doi (DE-627)SPR049629557 (SPR)s00213-023-06347-1-e DE-627 ger DE-627 rakwb eng Chestnykh, Daria verfasserin aut Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 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. DRD4 agonist (dpeaa)DE-He213 APH199 (dpeaa)DE-He213 Anxiety (dpeaa)DE-He213 Depression (dpeaa)DE-He213 Schizophrenia (dpeaa)DE-He213 Psychosis (dpeaa)DE-He213 Alcohol (dpeaa)DE-He213 Graßl, Fabian aut Pfeifer, Canice aut Dülk, Jonas aut Ebner, Chiara aut Walters, Mona aut von Hörsten, Stephan aut Kornhuber, Johannes aut Kalinichenko, Liubov S. aut Heinrich, Markus aut Müller, Christian P. aut Enthalten in Psychopharmacology Berlin : Springer, 1959 240(2023), 4 vom: 28. Feb., Seite 1011-1031 (DE-627)341342254 (DE-600)2066933-1 1432-2072 nnns volume:240 year:2023 number:4 day:28 month:02 pages:1011-1031 https://dx.doi.org/10.1007/s00213-023-06347-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 240 2023 4 28 02 1011-1031
spelling	10.1007/s00213-023-06347-1 doi (DE-627)SPR049629557 (SPR)s00213-023-06347-1-e DE-627 ger DE-627 rakwb eng Chestnykh, Daria verfasserin aut Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 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. DRD4 agonist (dpeaa)DE-He213 APH199 (dpeaa)DE-He213 Anxiety (dpeaa)DE-He213 Depression (dpeaa)DE-He213 Schizophrenia (dpeaa)DE-He213 Psychosis (dpeaa)DE-He213 Alcohol (dpeaa)DE-He213 Graßl, Fabian aut Pfeifer, Canice aut Dülk, Jonas aut Ebner, Chiara aut Walters, Mona aut von Hörsten, Stephan aut Kornhuber, Johannes aut Kalinichenko, Liubov S. aut Heinrich, Markus aut Müller, Christian P. aut Enthalten in Psychopharmacology Berlin : Springer, 1959 240(2023), 4 vom: 28. Feb., Seite 1011-1031 (DE-627)341342254 (DE-600)2066933-1 1432-2072 nnns volume:240 year:2023 number:4 day:28 month:02 pages:1011-1031 https://dx.doi.org/10.1007/s00213-023-06347-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 240 2023 4 28 02 1011-1031
allfields_unstemmed	10.1007/s00213-023-06347-1 doi (DE-627)SPR049629557 (SPR)s00213-023-06347-1-e DE-627 ger DE-627 rakwb eng Chestnykh, Daria verfasserin aut Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 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. DRD4 agonist (dpeaa)DE-He213 APH199 (dpeaa)DE-He213 Anxiety (dpeaa)DE-He213 Depression (dpeaa)DE-He213 Schizophrenia (dpeaa)DE-He213 Psychosis (dpeaa)DE-He213 Alcohol (dpeaa)DE-He213 Graßl, Fabian aut Pfeifer, Canice aut Dülk, Jonas aut Ebner, Chiara aut Walters, Mona aut von Hörsten, Stephan aut Kornhuber, Johannes aut Kalinichenko, Liubov S. aut Heinrich, Markus aut Müller, Christian P. aut Enthalten in Psychopharmacology Berlin : Springer, 1959 240(2023), 4 vom: 28. Feb., Seite 1011-1031 (DE-627)341342254 (DE-600)2066933-1 1432-2072 nnns volume:240 year:2023 number:4 day:28 month:02 pages:1011-1031 https://dx.doi.org/10.1007/s00213-023-06347-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 240 2023 4 28 02 1011-1031
allfieldsGer	10.1007/s00213-023-06347-1 doi (DE-627)SPR049629557 (SPR)s00213-023-06347-1-e DE-627 ger DE-627 rakwb eng Chestnykh, Daria verfasserin aut Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 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. DRD4 agonist (dpeaa)DE-He213 APH199 (dpeaa)DE-He213 Anxiety (dpeaa)DE-He213 Depression (dpeaa)DE-He213 Schizophrenia (dpeaa)DE-He213 Psychosis (dpeaa)DE-He213 Alcohol (dpeaa)DE-He213 Graßl, Fabian aut Pfeifer, Canice aut Dülk, Jonas aut Ebner, Chiara aut Walters, Mona aut von Hörsten, Stephan aut Kornhuber, Johannes aut Kalinichenko, Liubov S. aut Heinrich, Markus aut Müller, Christian P. aut Enthalten in Psychopharmacology Berlin : Springer, 1959 240(2023), 4 vom: 28. Feb., Seite 1011-1031 (DE-627)341342254 (DE-600)2066933-1 1432-2072 nnns volume:240 year:2023 number:4 day:28 month:02 pages:1011-1031 https://dx.doi.org/10.1007/s00213-023-06347-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 240 2023 4 28 02 1011-1031
allfieldsSound	10.1007/s00213-023-06347-1 doi (DE-627)SPR049629557 (SPR)s00213-023-06347-1-e DE-627 ger DE-627 rakwb eng Chestnykh, Daria verfasserin aut Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 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. DRD4 agonist (dpeaa)DE-He213 APH199 (dpeaa)DE-He213 Anxiety (dpeaa)DE-He213 Depression (dpeaa)DE-He213 Schizophrenia (dpeaa)DE-He213 Psychosis (dpeaa)DE-He213 Alcohol (dpeaa)DE-He213 Graßl, Fabian aut Pfeifer, Canice aut Dülk, Jonas aut Ebner, Chiara aut Walters, Mona aut von Hörsten, Stephan aut Kornhuber, Johannes aut Kalinichenko, Liubov S. aut Heinrich, Markus aut Müller, Christian P. aut Enthalten in Psychopharmacology Berlin : Springer, 1959 240(2023), 4 vom: 28. Feb., Seite 1011-1031 (DE-627)341342254 (DE-600)2066933-1 1432-2072 nnns volume:240 year:2023 number:4 day:28 month:02 pages:1011-1031 https://dx.doi.org/10.1007/s00213-023-06347-1 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 240 2023 4 28 02 1011-1031
language	English
source	Enthalten in Psychopharmacology 240(2023), 4 vom: 28. Feb., Seite 1011-1031 volume:240 year:2023 number:4 day:28 month:02 pages:1011-1031
sourceStr	Enthalten in Psychopharmacology 240(2023), 4 vom: 28. Feb., Seite 1011-1031 volume:240 year:2023 number:4 day:28 month:02 pages:1011-1031
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	DRD4 agonist APH199 Anxiety Depression Schizophrenia Psychosis Alcohol
isfreeaccess_bool	true
container_title	Psychopharmacology
authorswithroles_txt_mv	Chestnykh, Daria @@aut@@ Graßl, Fabian @@aut@@ Pfeifer, Canice @@aut@@ Dülk, Jonas @@aut@@ Ebner, Chiara @@aut@@ Walters, Mona @@aut@@ von Hörsten, Stephan @@aut@@ Kornhuber, Johannes @@aut@@ Kalinichenko, Liubov S. @@aut@@ Heinrich, Markus @@aut@@ Müller, Christian P. @@aut@@
publishDateDaySort_date	2023-02-28T00:00:00Z
hierarchy_top_id	341342254
id	SPR049629557
language_de	englisch
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author	Chestnykh, Daria
spellingShingle	Chestnykh, Daria misc DRD4 agonist misc APH199 misc Anxiety misc Depression misc Schizophrenia misc Psychosis misc Alcohol Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models
authorStr	Chestnykh, Daria
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topic_title	Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models DRD4 agonist (dpeaa)DE-He213 APH199 (dpeaa)DE-He213 Anxiety (dpeaa)DE-He213 Depression (dpeaa)DE-He213 Schizophrenia (dpeaa)DE-He213 Psychosis (dpeaa)DE-He213 Alcohol (dpeaa)DE-He213
topic	misc DRD4 agonist misc APH199 misc Anxiety misc Depression misc Schizophrenia misc Psychosis misc Alcohol
topic_unstemmed	misc DRD4 agonist misc APH199 misc Anxiety misc Depression misc Schizophrenia misc Psychosis misc Alcohol
topic_browse	misc DRD4 agonist misc APH199 misc Anxiety misc Depression misc Schizophrenia misc Psychosis misc Alcohol
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title	Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models
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title_full	Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models
author_sort	Chestnykh, Daria
journal	Psychopharmacology
journalStr	Psychopharmacology
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author_browse	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.
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author-letter	Chestnykh, Daria
doi_str_mv	10.1007/s00213-023-06347-1
title_sort	behavioural effects of aph199, a selective dopamine d4 receptor agonist, in animal models
title_auth	Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models
abstract	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. © The Author(s) 2023
abstractGer	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. © The Author(s) 2023
abstract_unstemmed	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. © The Author(s) 2023
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container_issue	4
title_short	Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models
url	https://dx.doi.org/10.1007/s00213-023-06347-1
remote_bool	true
author2	Graßl, Fabian Pfeifer, Canice Dülk, Jonas Ebner, Chiara Walters, Mona von Hörsten, Stephan Kornhuber, Johannes Kalinichenko, Liubov S. Heinrich, Markus Müller, Christian P.
author2Str	Graßl, Fabian Pfeifer, Canice Dülk, Jonas Ebner, Chiara Walters, Mona von Hörsten, Stephan Kornhuber, Johannes Kalinichenko, Liubov S. Heinrich, Markus Müller, Christian P.
ppnlink	341342254
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doi_str	10.1007/s00213-023-06347-1
up_date	2024-07-04T01:37:46.750Z
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Behavioural effects of APH199, a selective dopamine D4 receptor agonist, in animal models

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