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.
authors: Center for Behavioral Neuroscience, Heinrich Heine University Düsseldorf, Universitätsstr. 1, D-40225 Düsseldorf, Germany; Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Düsseldorf, Universitätsstr. 1, D-40225 Düsseldorf, Germany. Electronic address: david.petri@uni-duesseldorf.de.
authors: D
authors: D
authors: Petri
authors: Center for Behavioral Neuroscience, Heinrich Heine University Düsseldorf, Universitätsstr. 1, D-40225 Düsseldorf, Germany. Electronic address: desouza@uni-duesseldorf.de.
authors: M A
authors: MA
authors: de Souza Silva
authors: Center for Behavioral Neuroscience, Heinrich Heine University Düsseldorf, Universitätsstr. 1, D-40225 Düsseldorf, Germany. Electronic address: owenchao@gmail.com.
authors: O Y-H
authors: OY
authors: Chao
authors: Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Düsseldorf, Universitätsstr. 1, D-40225 Düsseldorf, Germany; Movement Disorders and Neuromodulation, Department of Neurology, University Hospital Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany. Electronic address: SchnitzA@med.uni-duesseldorf.de.
authors: A
authors: A
authors: Schnitzler
authors: Center for Behavioral Neuroscience, Heinrich Heine University Düsseldorf, Universitätsstr. 1, D-40225 Düsseldorf, Germany. Electronic address: jph@uni-duesseldorf.de.
authors: J P
authors: JP
authors: Huston
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D019964:Mood Disorders / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D016202:N-Methylaspartate / Q000633:toxicity; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000150:complications*; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D055139:Sensory Gating / Q000187:drug effects; D013687:Telencephalon / Q000378:metabolism*
chemical_list: D018663:Adrenergic Agents; D018690:Excitatory Amino Acid Agonists; D016202:N-Methylaspartate; D016627:Oxidopamine
keywords: 5-HT; Parkinson’s disease; anxiety; depression; mPFC; memory