Serotonergic interaction between medial prefrontal cortex and mesotelencephalic DA system underlies cognitive and affective deficits in hemiparkinsonian rats

D. Petri; M. A. de Souza Silva; O. Y.H. Chao; A. Schnitzler; J. P. Huston

doi:10.1016/j.neuroscience.2015.08.022

Serotonergic interaction between medial prefrontal cortex and mesotelencephalic DA system underlies cognitive and affective deficits in hemiparkinsonian rats

D. Petri, M. A. de Souza Silva, O. Y.H. Chao, A. Schnitzler, J. P. Huston

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Abstract

Parkinson's disease (PD) patients not only exhibit motor impairments, but also characteristic deficits in cognitive and affective functions. Such functions have consistently been associated with the medial prefrontal cortex (mPFC). To determine whether there is an interaction between the midbrain dopamine system (MDS) and the mPFC underlying the cognitive and emotional deficits seen in rats, we administered a disconnection procedure of these structures by applying lesions to the mPFC (N-methyl-. d-aspartic acid (NMDA)) and the medial forebrain bundle (6-hydroxydopamine (6-OHDA)) either in the same or opposite hemispheres. The results indicate a functional interaction of the MDS and the mPFC: Disconnection effects on behavior were observed with respect to memory-, anxiety- and depression-related behaviors. A disconnection of the mPFC and MDS had promnestic, antidepressant- and anxiolytic-like effects. In order to determine whether this circuit between the mPFC and MDS involves serotonergic mechanisms, we also utilized serotonin-specific disconnections of the mPFC by applying the 5-HT-specific agent 5,7-dihydroxytryptamine (5,7-DHT) into the mPFC and 6-OHDA into the medial forebrain bundle, again either in the same or opposite hemispheres. The behavioral effects observed here resembled those incurred by the unspecific disconnection of the mPFC, demonstrating a significant contribution of serotonergic mechanisms to the interplay between the MDS and the mPFC. Taken together, these experiments provide evidence for an interaction of the MDS and the mPFC in the control of cognitive and affective processes known to be impaired in PD and point toward a prominent involvement of the serotonergic system. A disconnection of the mPFC and the MDS had promnestic, antidepressant- and anxiolytic-like behavioral effects. These findings may impact therapeutic approaches in the treatment of cognitive and neuropsychiatric symptoms seen in PD.

Original language	English (US)
Pages (from-to)	51-63
Number of pages	13
Journal	Neuroscience
Volume	307
DOIs	https://doi.org/10.1016/j.neuroscience.2015.08.022
State	Published - Oct 29 2015
Externally published	Yes

Bibliographical note

Funding Information:
This project was supported by a grant provided by the Interdisciplinary Graduate School for Brain Research and Translational Neuroscience ( iBrain ) of the Neuroscience Network Düsseldorf (NND). M.A. de Souza Silva was supported by a Heisenberg Fellowship SO 1032/5-1 and EU-FP7 (MC-ITN-“In-SENS”-ESR7 607616). J.P.H. was supported by DFG Grant HU 306/27-3 . The funding sources had no involvement in study design, in the collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the article for publication. The authors declare no competing financial interests.

Publisher Copyright:
© 2015 IBRO.

Keywords

5-HT
Anxiety
Depression
Memory
MPFC
Parkinson's disease

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title = "Serotonergic interaction between medial prefrontal cortex and mesotelencephalic DA system underlies cognitive and affective deficits in hemiparkinsonian rats",

abstract = "Parkinson's disease (PD) patients not only exhibit motor impairments, but also characteristic deficits in cognitive and affective functions. Such functions have consistently been associated with the medial prefrontal cortex (mPFC). To determine whether there is an interaction between the midbrain dopamine system (MDS) and the mPFC underlying the cognitive and emotional deficits seen in rats, we administered a disconnection procedure of these structures by applying lesions to the mPFC (N-methyl-. d-aspartic acid (NMDA)) and the medial forebrain bundle (6-hydroxydopamine (6-OHDA)) either in the same or opposite hemispheres. The results indicate a functional interaction of the MDS and the mPFC: Disconnection effects on behavior were observed with respect to memory-, anxiety- and depression-related behaviors. A disconnection of the mPFC and MDS had promnestic, antidepressant- and anxiolytic-like effects. In order to determine whether this circuit between the mPFC and MDS involves serotonergic mechanisms, we also utilized serotonin-specific disconnections of the mPFC by applying the 5-HT-specific agent 5,7-dihydroxytryptamine (5,7-DHT) into the mPFC and 6-OHDA into the medial forebrain bundle, again either in the same or opposite hemispheres. The behavioral effects observed here resembled those incurred by the unspecific disconnection of the mPFC, demonstrating a significant contribution of serotonergic mechanisms to the interplay between the MDS and the mPFC. Taken together, these experiments provide evidence for an interaction of the MDS and the mPFC in the control of cognitive and affective processes known to be impaired in PD and point toward a prominent involvement of the serotonergic system. A disconnection of the mPFC and the MDS had promnestic, antidepressant- and anxiolytic-like behavioral effects. These findings may impact therapeutic approaches in the treatment of cognitive and neuropsychiatric symptoms seen in PD.",

keywords = "5-HT, Anxiety, Depression, Memory, MPFC, Parkinson's disease",

author = "D. Petri and {de Souza Silva}, {M. A.} and Chao, {O. Y.H.} and A. Schnitzler and Huston, {J. P.}",

note = "Funding Information: This project was supported by a grant provided by the Interdisciplinary Graduate School for Brain Research and Translational Neuroscience ( iBrain ) of the Neuroscience Network D{\"u}sseldorf (NND). M.A. de Souza Silva was supported by a Heisenberg Fellowship SO 1032/5-1 and EU-FP7 (MC-ITN-“In-SENS”-ESR7 607616). J.P.H. was supported by DFG Grant HU 306/27-3 . The funding sources had no involvement in study design, in the collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the article for publication. The authors declare no competing financial interests. Publisher Copyright: {\textcopyright} 2015 IBRO.",

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doi = "10.1016/j.neuroscience.2015.08.022",

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AU - Petri, D.

AU - de Souza Silva, M. A.

AU - Chao, O. Y.H.

AU - Schnitzler, A.

AU - Huston, J. P.

N1 - Funding Information: This project was supported by a grant provided by the Interdisciplinary Graduate School for Brain Research and Translational Neuroscience ( iBrain ) of the Neuroscience Network Düsseldorf (NND). M.A. de Souza Silva was supported by a Heisenberg Fellowship SO 1032/5-1 and EU-FP7 (MC-ITN-“In-SENS”-ESR7 607616). J.P.H. was supported by DFG Grant HU 306/27-3 . The funding sources had no involvement in study design, in the collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the article for publication. The authors declare no competing financial interests. Publisher Copyright: © 2015 IBRO.

PY - 2015/10/29

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N2 - Parkinson's disease (PD) patients not only exhibit motor impairments, but also characteristic deficits in cognitive and affective functions. Such functions have consistently been associated with the medial prefrontal cortex (mPFC). To determine whether there is an interaction between the midbrain dopamine system (MDS) and the mPFC underlying the cognitive and emotional deficits seen in rats, we administered a disconnection procedure of these structures by applying lesions to the mPFC (N-methyl-. d-aspartic acid (NMDA)) and the medial forebrain bundle (6-hydroxydopamine (6-OHDA)) either in the same or opposite hemispheres. The results indicate a functional interaction of the MDS and the mPFC: Disconnection effects on behavior were observed with respect to memory-, anxiety- and depression-related behaviors. A disconnection of the mPFC and MDS had promnestic, antidepressant- and anxiolytic-like effects. In order to determine whether this circuit between the mPFC and MDS involves serotonergic mechanisms, we also utilized serotonin-specific disconnections of the mPFC by applying the 5-HT-specific agent 5,7-dihydroxytryptamine (5,7-DHT) into the mPFC and 6-OHDA into the medial forebrain bundle, again either in the same or opposite hemispheres. The behavioral effects observed here resembled those incurred by the unspecific disconnection of the mPFC, demonstrating a significant contribution of serotonergic mechanisms to the interplay between the MDS and the mPFC. Taken together, these experiments provide evidence for an interaction of the MDS and the mPFC in the control of cognitive and affective processes known to be impaired in PD and point toward a prominent involvement of the serotonergic system. A disconnection of the mPFC and the MDS had promnestic, antidepressant- and anxiolytic-like behavioral effects. These findings may impact therapeutic approaches in the treatment of cognitive and neuropsychiatric symptoms seen in PD.

AB - Parkinson's disease (PD) patients not only exhibit motor impairments, but also characteristic deficits in cognitive and affective functions. Such functions have consistently been associated with the medial prefrontal cortex (mPFC). To determine whether there is an interaction between the midbrain dopamine system (MDS) and the mPFC underlying the cognitive and emotional deficits seen in rats, we administered a disconnection procedure of these structures by applying lesions to the mPFC (N-methyl-. d-aspartic acid (NMDA)) and the medial forebrain bundle (6-hydroxydopamine (6-OHDA)) either in the same or opposite hemispheres. The results indicate a functional interaction of the MDS and the mPFC: Disconnection effects on behavior were observed with respect to memory-, anxiety- and depression-related behaviors. A disconnection of the mPFC and MDS had promnestic, antidepressant- and anxiolytic-like effects. In order to determine whether this circuit between the mPFC and MDS involves serotonergic mechanisms, we also utilized serotonin-specific disconnections of the mPFC by applying the 5-HT-specific agent 5,7-dihydroxytryptamine (5,7-DHT) into the mPFC and 6-OHDA into the medial forebrain bundle, again either in the same or opposite hemispheres. The behavioral effects observed here resembled those incurred by the unspecific disconnection of the mPFC, demonstrating a significant contribution of serotonergic mechanisms to the interplay between the MDS and the mPFC. Taken together, these experiments provide evidence for an interaction of the MDS and the mPFC in the control of cognitive and affective processes known to be impaired in PD and point toward a prominent involvement of the serotonergic system. A disconnection of the mPFC and the MDS had promnestic, antidepressant- and anxiolytic-like behavioral effects. These findings may impact therapeutic approaches in the treatment of cognitive and neuropsychiatric symptoms seen in PD.

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Serotonergic interaction between medial prefrontal cortex and mesotelencephalic DA system underlies cognitive and affective deficits in hemiparkinsonian rats

Abstract

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Keywords

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