Social defeat-induced anhedonia: effects on operant sucrose-seeking behavior

Reduced capacity to experience pleasure, also known as anhedonia, is a key feature of the depressive state and is associated with poor disease prognosis and treatment outcome. Various behavioral readouts (e.g. reduced sucrose intake) have been employed in animal models of depression as a measure of anhedonia. However, several aspects of anhedonia are poorly represented within the repertoire of current preclinical assessments. We recently adopted the social defeat-induced persistent stress (SDPS) paradigm that models a maintained depressive-like state in the rat, including social withdrawal and deficits in short-term spatial memory. Here we investigated whether SDPS elicited persistent deficits in natural reward evaluation, as part of anhedonia. We examined cue-paired operant sucrose self-administration, enabling us to study acquisition, motivation, extinction and relapse to sucrose seeking following SDPS. Furthermore, we addressed whether guanfacine, an α2-adrenergic agonist that reduces stress-triggered maladaptive behavioral responses to drugs of abuse, could relief from SDPS-induced anhedonia. SDPS, consisting of 5 social defeat episodes followed by prolonged (≥8 weeks) social isolation, did not affect sucrose consumption during acquisition of self-administration. However, it strongly enhanced the motivational drive to acquire a sucrose reward in progressive ratio training. Moreover, SDPS induced initial resilience to extinction and rendered animals more sensitive to cue-induced reinstatement of sucrose-seeking. Guanfacine treatment attenuated SDPS-induced motivational overdrive and limited reinstatement of sucrose seeking, normalizing behavior to control levels. Together, our data indicate that long after the termination of stress exposure, SDPS induces guanfacine-reversible deficits in evaluation of a natural reward. Importantly, the SDPS-triggered anhedonia reflects many aspects of the human phenotype, including impaired motivation and goal-directed conduct. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Danai eRiga [verfasserIn] J. Trisna Theijs [verfasserIn] Taco J De Vries [verfasserIn] August B Smit [verfasserIn] Sabine eSpijker [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2015

Schlagwörter:	Anhedonia Depression Guanfacine Sucrose self-administration Social defeat-induced persistent stress (SDPS)

Übergeordnetes Werk:	In: Frontiers in Behavioral Neuroscience - Frontiers Media S.A., 2008, 9(2015)
Übergeordnetes Werk:	volume:9 ; year:2015

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fnbeh.2015.00195

Katalog-ID:	DOAJ002865793

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allfields	10.3389/fnbeh.2015.00195 doi (DE-627)DOAJ002865793 (DE-599)DOAJca893861cc444f70bc8305c399545523 DE-627 ger DE-627 rakwb eng RC321-571 Danai eRiga verfasserin aut Social defeat-induced anhedonia: effects on operant sucrose-seeking behavior 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Reduced capacity to experience pleasure, also known as anhedonia, is a key feature of the depressive state and is associated with poor disease prognosis and treatment outcome. Various behavioral readouts (e.g. reduced sucrose intake) have been employed in animal models of depression as a measure of anhedonia. However, several aspects of anhedonia are poorly represented within the repertoire of current preclinical assessments. We recently adopted the social defeat-induced persistent stress (SDPS) paradigm that models a maintained depressive-like state in the rat, including social withdrawal and deficits in short-term spatial memory. Here we investigated whether SDPS elicited persistent deficits in natural reward evaluation, as part of anhedonia. We examined cue-paired operant sucrose self-administration, enabling us to study acquisition, motivation, extinction and relapse to sucrose seeking following SDPS. Furthermore, we addressed whether guanfacine, an α2-adrenergic agonist that reduces stress-triggered maladaptive behavioral responses to drugs of abuse, could relief from SDPS-induced anhedonia. SDPS, consisting of 5 social defeat episodes followed by prolonged (≥8 weeks) social isolation, did not affect sucrose consumption during acquisition of self-administration. However, it strongly enhanced the motivational drive to acquire a sucrose reward in progressive ratio training. Moreover, SDPS induced initial resilience to extinction and rendered animals more sensitive to cue-induced reinstatement of sucrose-seeking. Guanfacine treatment attenuated SDPS-induced motivational overdrive and limited reinstatement of sucrose seeking, normalizing behavior to control levels. Together, our data indicate that long after the termination of stress exposure, SDPS induces guanfacine-reversible deficits in evaluation of a natural reward. Importantly, the SDPS-triggered anhedonia reflects many aspects of the human phenotype, including impaired motivation and goal-directed conduct. Anhedonia Depression Guanfacine Sucrose self-administration Social defeat-induced persistent stress (SDPS) Neurosciences. Biological psychiatry. Neuropsychiatry J. Trisna Theijs verfasserin aut Taco J De Vries verfasserin aut Taco J De Vries verfasserin aut August B Smit verfasserin aut Sabine eSpijker verfasserin aut In Frontiers in Behavioral Neuroscience Frontiers Media S.A., 2008 9(2015) (DE-627)579826392 (DE-600)2452960-6 16625153 nnns volume:9 year:2015 https://doi.org/10.3389/fnbeh.2015.00195 kostenfrei https://doaj.org/article/ca893861cc444f70bc8305c399545523 kostenfrei http://journal.frontiersin.org/Journal/10.3389/fnbeh.2015.00195/full kostenfrei https://doaj.org/toc/1662-5153 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2015
spelling	10.3389/fnbeh.2015.00195 doi (DE-627)DOAJ002865793 (DE-599)DOAJca893861cc444f70bc8305c399545523 DE-627 ger DE-627 rakwb eng RC321-571 Danai eRiga verfasserin aut Social defeat-induced anhedonia: effects on operant sucrose-seeking behavior 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Reduced capacity to experience pleasure, also known as anhedonia, is a key feature of the depressive state and is associated with poor disease prognosis and treatment outcome. Various behavioral readouts (e.g. reduced sucrose intake) have been employed in animal models of depression as a measure of anhedonia. However, several aspects of anhedonia are poorly represented within the repertoire of current preclinical assessments. We recently adopted the social defeat-induced persistent stress (SDPS) paradigm that models a maintained depressive-like state in the rat, including social withdrawal and deficits in short-term spatial memory. Here we investigated whether SDPS elicited persistent deficits in natural reward evaluation, as part of anhedonia. We examined cue-paired operant sucrose self-administration, enabling us to study acquisition, motivation, extinction and relapse to sucrose seeking following SDPS. Furthermore, we addressed whether guanfacine, an α2-adrenergic agonist that reduces stress-triggered maladaptive behavioral responses to drugs of abuse, could relief from SDPS-induced anhedonia. SDPS, consisting of 5 social defeat episodes followed by prolonged (≥8 weeks) social isolation, did not affect sucrose consumption during acquisition of self-administration. However, it strongly enhanced the motivational drive to acquire a sucrose reward in progressive ratio training. Moreover, SDPS induced initial resilience to extinction and rendered animals more sensitive to cue-induced reinstatement of sucrose-seeking. Guanfacine treatment attenuated SDPS-induced motivational overdrive and limited reinstatement of sucrose seeking, normalizing behavior to control levels. Together, our data indicate that long after the termination of stress exposure, SDPS induces guanfacine-reversible deficits in evaluation of a natural reward. Importantly, the SDPS-triggered anhedonia reflects many aspects of the human phenotype, including impaired motivation and goal-directed conduct. Anhedonia Depression Guanfacine Sucrose self-administration Social defeat-induced persistent stress (SDPS) Neurosciences. Biological psychiatry. Neuropsychiatry J. Trisna Theijs verfasserin aut Taco J De Vries verfasserin aut Taco J De Vries verfasserin aut August B Smit verfasserin aut Sabine eSpijker verfasserin aut In Frontiers in Behavioral Neuroscience Frontiers Media S.A., 2008 9(2015) (DE-627)579826392 (DE-600)2452960-6 16625153 nnns volume:9 year:2015 https://doi.org/10.3389/fnbeh.2015.00195 kostenfrei https://doaj.org/article/ca893861cc444f70bc8305c399545523 kostenfrei http://journal.frontiersin.org/Journal/10.3389/fnbeh.2015.00195/full kostenfrei https://doaj.org/toc/1662-5153 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2015
allfields_unstemmed	10.3389/fnbeh.2015.00195 doi (DE-627)DOAJ002865793 (DE-599)DOAJca893861cc444f70bc8305c399545523 DE-627 ger DE-627 rakwb eng RC321-571 Danai eRiga verfasserin aut Social defeat-induced anhedonia: effects on operant sucrose-seeking behavior 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Reduced capacity to experience pleasure, also known as anhedonia, is a key feature of the depressive state and is associated with poor disease prognosis and treatment outcome. Various behavioral readouts (e.g. reduced sucrose intake) have been employed in animal models of depression as a measure of anhedonia. However, several aspects of anhedonia are poorly represented within the repertoire of current preclinical assessments. We recently adopted the social defeat-induced persistent stress (SDPS) paradigm that models a maintained depressive-like state in the rat, including social withdrawal and deficits in short-term spatial memory. Here we investigated whether SDPS elicited persistent deficits in natural reward evaluation, as part of anhedonia. We examined cue-paired operant sucrose self-administration, enabling us to study acquisition, motivation, extinction and relapse to sucrose seeking following SDPS. Furthermore, we addressed whether guanfacine, an α2-adrenergic agonist that reduces stress-triggered maladaptive behavioral responses to drugs of abuse, could relief from SDPS-induced anhedonia. SDPS, consisting of 5 social defeat episodes followed by prolonged (≥8 weeks) social isolation, did not affect sucrose consumption during acquisition of self-administration. However, it strongly enhanced the motivational drive to acquire a sucrose reward in progressive ratio training. Moreover, SDPS induced initial resilience to extinction and rendered animals more sensitive to cue-induced reinstatement of sucrose-seeking. Guanfacine treatment attenuated SDPS-induced motivational overdrive and limited reinstatement of sucrose seeking, normalizing behavior to control levels. Together, our data indicate that long after the termination of stress exposure, SDPS induces guanfacine-reversible deficits in evaluation of a natural reward. Importantly, the SDPS-triggered anhedonia reflects many aspects of the human phenotype, including impaired motivation and goal-directed conduct. Anhedonia Depression Guanfacine Sucrose self-administration Social defeat-induced persistent stress (SDPS) Neurosciences. Biological psychiatry. Neuropsychiatry J. Trisna Theijs verfasserin aut Taco J De Vries verfasserin aut Taco J De Vries verfasserin aut August B Smit verfasserin aut Sabine eSpijker verfasserin aut In Frontiers in Behavioral Neuroscience Frontiers Media S.A., 2008 9(2015) (DE-627)579826392 (DE-600)2452960-6 16625153 nnns volume:9 year:2015 https://doi.org/10.3389/fnbeh.2015.00195 kostenfrei https://doaj.org/article/ca893861cc444f70bc8305c399545523 kostenfrei http://journal.frontiersin.org/Journal/10.3389/fnbeh.2015.00195/full kostenfrei https://doaj.org/toc/1662-5153 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2015
allfieldsGer	10.3389/fnbeh.2015.00195 doi (DE-627)DOAJ002865793 (DE-599)DOAJca893861cc444f70bc8305c399545523 DE-627 ger DE-627 rakwb eng RC321-571 Danai eRiga verfasserin aut Social defeat-induced anhedonia: effects on operant sucrose-seeking behavior 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Reduced capacity to experience pleasure, also known as anhedonia, is a key feature of the depressive state and is associated with poor disease prognosis and treatment outcome. Various behavioral readouts (e.g. reduced sucrose intake) have been employed in animal models of depression as a measure of anhedonia. However, several aspects of anhedonia are poorly represented within the repertoire of current preclinical assessments. We recently adopted the social defeat-induced persistent stress (SDPS) paradigm that models a maintained depressive-like state in the rat, including social withdrawal and deficits in short-term spatial memory. Here we investigated whether SDPS elicited persistent deficits in natural reward evaluation, as part of anhedonia. We examined cue-paired operant sucrose self-administration, enabling us to study acquisition, motivation, extinction and relapse to sucrose seeking following SDPS. Furthermore, we addressed whether guanfacine, an α2-adrenergic agonist that reduces stress-triggered maladaptive behavioral responses to drugs of abuse, could relief from SDPS-induced anhedonia. SDPS, consisting of 5 social defeat episodes followed by prolonged (≥8 weeks) social isolation, did not affect sucrose consumption during acquisition of self-administration. However, it strongly enhanced the motivational drive to acquire a sucrose reward in progressive ratio training. Moreover, SDPS induced initial resilience to extinction and rendered animals more sensitive to cue-induced reinstatement of sucrose-seeking. Guanfacine treatment attenuated SDPS-induced motivational overdrive and limited reinstatement of sucrose seeking, normalizing behavior to control levels. Together, our data indicate that long after the termination of stress exposure, SDPS induces guanfacine-reversible deficits in evaluation of a natural reward. Importantly, the SDPS-triggered anhedonia reflects many aspects of the human phenotype, including impaired motivation and goal-directed conduct. Anhedonia Depression Guanfacine Sucrose self-administration Social defeat-induced persistent stress (SDPS) Neurosciences. Biological psychiatry. Neuropsychiatry J. Trisna Theijs verfasserin aut Taco J De Vries verfasserin aut Taco J De Vries verfasserin aut August B Smit verfasserin aut Sabine eSpijker verfasserin aut In Frontiers in Behavioral Neuroscience Frontiers Media S.A., 2008 9(2015) (DE-627)579826392 (DE-600)2452960-6 16625153 nnns volume:9 year:2015 https://doi.org/10.3389/fnbeh.2015.00195 kostenfrei https://doaj.org/article/ca893861cc444f70bc8305c399545523 kostenfrei http://journal.frontiersin.org/Journal/10.3389/fnbeh.2015.00195/full kostenfrei https://doaj.org/toc/1662-5153 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2015
allfieldsSound	10.3389/fnbeh.2015.00195 doi (DE-627)DOAJ002865793 (DE-599)DOAJca893861cc444f70bc8305c399545523 DE-627 ger DE-627 rakwb eng RC321-571 Danai eRiga verfasserin aut Social defeat-induced anhedonia: effects on operant sucrose-seeking behavior 2015 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Reduced capacity to experience pleasure, also known as anhedonia, is a key feature of the depressive state and is associated with poor disease prognosis and treatment outcome. Various behavioral readouts (e.g. reduced sucrose intake) have been employed in animal models of depression as a measure of anhedonia. However, several aspects of anhedonia are poorly represented within the repertoire of current preclinical assessments. We recently adopted the social defeat-induced persistent stress (SDPS) paradigm that models a maintained depressive-like state in the rat, including social withdrawal and deficits in short-term spatial memory. Here we investigated whether SDPS elicited persistent deficits in natural reward evaluation, as part of anhedonia. We examined cue-paired operant sucrose self-administration, enabling us to study acquisition, motivation, extinction and relapse to sucrose seeking following SDPS. Furthermore, we addressed whether guanfacine, an α2-adrenergic agonist that reduces stress-triggered maladaptive behavioral responses to drugs of abuse, could relief from SDPS-induced anhedonia. SDPS, consisting of 5 social defeat episodes followed by prolonged (≥8 weeks) social isolation, did not affect sucrose consumption during acquisition of self-administration. However, it strongly enhanced the motivational drive to acquire a sucrose reward in progressive ratio training. Moreover, SDPS induced initial resilience to extinction and rendered animals more sensitive to cue-induced reinstatement of sucrose-seeking. Guanfacine treatment attenuated SDPS-induced motivational overdrive and limited reinstatement of sucrose seeking, normalizing behavior to control levels. Together, our data indicate that long after the termination of stress exposure, SDPS induces guanfacine-reversible deficits in evaluation of a natural reward. Importantly, the SDPS-triggered anhedonia reflects many aspects of the human phenotype, including impaired motivation and goal-directed conduct. Anhedonia Depression Guanfacine Sucrose self-administration Social defeat-induced persistent stress (SDPS) Neurosciences. Biological psychiatry. Neuropsychiatry J. Trisna Theijs verfasserin aut Taco J De Vries verfasserin aut Taco J De Vries verfasserin aut August B Smit verfasserin aut Sabine eSpijker verfasserin aut In Frontiers in Behavioral Neuroscience Frontiers Media S.A., 2008 9(2015) (DE-627)579826392 (DE-600)2452960-6 16625153 nnns volume:9 year:2015 https://doi.org/10.3389/fnbeh.2015.00195 kostenfrei https://doaj.org/article/ca893861cc444f70bc8305c399545523 kostenfrei http://journal.frontiersin.org/Journal/10.3389/fnbeh.2015.00195/full kostenfrei https://doaj.org/toc/1662-5153 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2015
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topic_facet	Anhedonia Depression Guanfacine Sucrose self-administration Social defeat-induced persistent stress (SDPS) Neurosciences. Biological psychiatry. Neuropsychiatry
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callnumber-first	R - Medicine
author	Danai eRiga
spellingShingle	Danai eRiga misc RC321-571 misc Anhedonia misc Depression misc Guanfacine misc Sucrose self-administration misc Social defeat-induced persistent stress (SDPS) misc Neurosciences. Biological psychiatry. Neuropsychiatry Social defeat-induced anhedonia: effects on operant sucrose-seeking behavior
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topic_title	RC321-571 Social defeat-induced anhedonia: effects on operant sucrose-seeking behavior Anhedonia Depression Guanfacine Sucrose self-administration Social defeat-induced persistent stress (SDPS)
topic	misc RC321-571 misc Anhedonia misc Depression misc Guanfacine misc Sucrose self-administration misc Social defeat-induced persistent stress (SDPS) misc Neurosciences. Biological psychiatry. Neuropsychiatry
topic_unstemmed	misc RC321-571 misc Anhedonia misc Depression misc Guanfacine misc Sucrose self-administration misc Social defeat-induced persistent stress (SDPS) misc Neurosciences. Biological psychiatry. Neuropsychiatry
topic_browse	misc RC321-571 misc Anhedonia misc Depression misc Guanfacine misc Sucrose self-administration misc Social defeat-induced persistent stress (SDPS) misc Neurosciences. Biological psychiatry. Neuropsychiatry
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title	Social defeat-induced anhedonia: effects on operant sucrose-seeking behavior
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title_sort	social defeat-induced anhedonia: effects on operant sucrose-seeking behavior
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title_auth	Social defeat-induced anhedonia: effects on operant sucrose-seeking behavior
abstract	Reduced capacity to experience pleasure, also known as anhedonia, is a key feature of the depressive state and is associated with poor disease prognosis and treatment outcome. Various behavioral readouts (e.g. reduced sucrose intake) have been employed in animal models of depression as a measure of anhedonia. However, several aspects of anhedonia are poorly represented within the repertoire of current preclinical assessments. We recently adopted the social defeat-induced persistent stress (SDPS) paradigm that models a maintained depressive-like state in the rat, including social withdrawal and deficits in short-term spatial memory. Here we investigated whether SDPS elicited persistent deficits in natural reward evaluation, as part of anhedonia. We examined cue-paired operant sucrose self-administration, enabling us to study acquisition, motivation, extinction and relapse to sucrose seeking following SDPS. Furthermore, we addressed whether guanfacine, an α2-adrenergic agonist that reduces stress-triggered maladaptive behavioral responses to drugs of abuse, could relief from SDPS-induced anhedonia. SDPS, consisting of 5 social defeat episodes followed by prolonged (≥8 weeks) social isolation, did not affect sucrose consumption during acquisition of self-administration. However, it strongly enhanced the motivational drive to acquire a sucrose reward in progressive ratio training. Moreover, SDPS induced initial resilience to extinction and rendered animals more sensitive to cue-induced reinstatement of sucrose-seeking. Guanfacine treatment attenuated SDPS-induced motivational overdrive and limited reinstatement of sucrose seeking, normalizing behavior to control levels. Together, our data indicate that long after the termination of stress exposure, SDPS induces guanfacine-reversible deficits in evaluation of a natural reward. Importantly, the SDPS-triggered anhedonia reflects many aspects of the human phenotype, including impaired motivation and goal-directed conduct.
abstractGer	Reduced capacity to experience pleasure, also known as anhedonia, is a key feature of the depressive state and is associated with poor disease prognosis and treatment outcome. Various behavioral readouts (e.g. reduced sucrose intake) have been employed in animal models of depression as a measure of anhedonia. However, several aspects of anhedonia are poorly represented within the repertoire of current preclinical assessments. We recently adopted the social defeat-induced persistent stress (SDPS) paradigm that models a maintained depressive-like state in the rat, including social withdrawal and deficits in short-term spatial memory. Here we investigated whether SDPS elicited persistent deficits in natural reward evaluation, as part of anhedonia. We examined cue-paired operant sucrose self-administration, enabling us to study acquisition, motivation, extinction and relapse to sucrose seeking following SDPS. Furthermore, we addressed whether guanfacine, an α2-adrenergic agonist that reduces stress-triggered maladaptive behavioral responses to drugs of abuse, could relief from SDPS-induced anhedonia. SDPS, consisting of 5 social defeat episodes followed by prolonged (≥8 weeks) social isolation, did not affect sucrose consumption during acquisition of self-administration. However, it strongly enhanced the motivational drive to acquire a sucrose reward in progressive ratio training. Moreover, SDPS induced initial resilience to extinction and rendered animals more sensitive to cue-induced reinstatement of sucrose-seeking. Guanfacine treatment attenuated SDPS-induced motivational overdrive and limited reinstatement of sucrose seeking, normalizing behavior to control levels. Together, our data indicate that long after the termination of stress exposure, SDPS induces guanfacine-reversible deficits in evaluation of a natural reward. Importantly, the SDPS-triggered anhedonia reflects many aspects of the human phenotype, including impaired motivation and goal-directed conduct.
abstract_unstemmed	Reduced capacity to experience pleasure, also known as anhedonia, is a key feature of the depressive state and is associated with poor disease prognosis and treatment outcome. Various behavioral readouts (e.g. reduced sucrose intake) have been employed in animal models of depression as a measure of anhedonia. However, several aspects of anhedonia are poorly represented within the repertoire of current preclinical assessments. We recently adopted the social defeat-induced persistent stress (SDPS) paradigm that models a maintained depressive-like state in the rat, including social withdrawal and deficits in short-term spatial memory. Here we investigated whether SDPS elicited persistent deficits in natural reward evaluation, as part of anhedonia. We examined cue-paired operant sucrose self-administration, enabling us to study acquisition, motivation, extinction and relapse to sucrose seeking following SDPS. Furthermore, we addressed whether guanfacine, an α2-adrenergic agonist that reduces stress-triggered maladaptive behavioral responses to drugs of abuse, could relief from SDPS-induced anhedonia. SDPS, consisting of 5 social defeat episodes followed by prolonged (≥8 weeks) social isolation, did not affect sucrose consumption during acquisition of self-administration. However, it strongly enhanced the motivational drive to acquire a sucrose reward in progressive ratio training. Moreover, SDPS induced initial resilience to extinction and rendered animals more sensitive to cue-induced reinstatement of sucrose-seeking. Guanfacine treatment attenuated SDPS-induced motivational overdrive and limited reinstatement of sucrose seeking, normalizing behavior to control levels. Together, our data indicate that long after the termination of stress exposure, SDPS induces guanfacine-reversible deficits in evaluation of a natural reward. Importantly, the SDPS-triggered anhedonia reflects many aspects of the human phenotype, including impaired motivation and goal-directed conduct.
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title_short	Social defeat-induced anhedonia: effects on operant sucrose-seeking behavior
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SDPS, consisting of 5 social defeat episodes followed by prolonged (≥8 weeks) social isolation, did not affect sucrose consumption during acquisition of self-administration. However, it strongly enhanced the motivational drive to acquire a sucrose reward in progressive ratio training. Moreover, SDPS induced initial resilience to extinction and rendered animals more sensitive to cue-induced reinstatement of sucrose-seeking. Guanfacine treatment attenuated SDPS-induced motivational overdrive and limited reinstatement of sucrose seeking, normalizing behavior to control levels. Together, our data indicate that long after the termination of stress exposure, SDPS induces guanfacine-reversible deficits in evaluation of a natural reward. 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Social defeat-induced anhedonia: effects on operant sucrose-seeking behavior

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