Increased electrical and metabolic activity in the dorsal raphe nucleus of Parkinsonian rats

Serotonin (5-HT) containing neurons in the dorsal raphe nucleus (DRN) may play important roles in Parkinson's disease (PD). This study investigated neural and metabolic activity of the DRN in animal PD models based on dopamine depletion. The data show both increased firing rate of DRN 5-HT neurons and increased cytochrome oxidase activity in dopamine-depleted rats, as compared to controls. These data support the hypothesis that the DRN 5-HT system is hyperactive in the dopamine-depleted brain.

[1]  G. Breese,et al.  Behavioral differences between neonatal and adult 6-hydroxydopamine-treated rats to dopamine agonists: relevance to neurological symptoms in clinical syndromes with reduced brain dopamine. , 1984, The Journal of pharmacology and experimental therapeutics.

[2]  Allan E. Johnson,et al.  Influence of electrical stimulation of the substantia nigra on spontaneous activity of raphe neurons in the anesthetized rat , 1979, Brain Research Bulletin.

[3]  Udo Rüb,et al.  Where Does Parkinson Disease Pathology Begin in the Brain? , 2002, Journal of neuropathology and experimental neurology.

[4]  T. Reader,et al.  Effects of denervation and hyperinnervation on dopamine and serotonin systems in the rat neostriatum: implications for human Parkinson's disease. , 1999, Neurochemistry international.

[5]  Roger B. H. Tootell,et al.  Modified technique for cytochrome oxidase histochemistry: increased staining intensity and compatibility with 2-deoxyglucose autoradiography , 1987, Journal of Neuroscience Methods.

[6]  T. Sharp,et al.  Neurochemical and anatomical identification of fast- and slow-firing neurones in the rat dorsal raphe nucleus using juxtacellular labelling methods in vivo , 2003, Neuroscience.

[7]  F. Zhou,et al.  Serotonergic sprouting is induced by dopamine-lesion in substantia nigra of adult rat brain , 1991, Brain Research.

[8]  Anders Björklund,et al.  Dopamine released from 5-HT terminals is the cause of L-DOPA-induced dyskinesia in parkinsonian rats. , 2007, Brain : a journal of neurology.

[9]  M. Kas,et al.  Alterations in serotonin signalling are involved in the hyperactivity of Pitx3‐deficient mice , 2008, The European journal of neuroscience.

[10]  J. Obeso,et al.  Motor behavioural changes after intracerebroventricular injection of 6-hydroxydopamine in the rat: an animal model of Parkinson's disease , 2001, Behavioural Brain Research.

[11]  C. Hammond,et al.  Dual Effect of High-Frequency Stimulation on Subthalamic Neuron Activity , 2003, The Journal of Neuroscience.

[12]  H. Steinbusch,et al.  Inhibition of 5-HT neuron activity and induction of depressive-like behavior by high-frequency stimulation of the subthalamic nucleus , 2007, Proceedings of the National Academy of Sciences.

[13]  T. Sharp,et al.  Evidence that central 5‐HT2A and 5‐HT2B/C receptors regulate 5‐HT cell firing in the dorsal raphe nucleus of the anaesthetised rat , 2003, British journal of pharmacology.

[14]  L. Seiden,et al.  Variability among brain regions in the specificity of 6-hydroxydopamine (6-OHDA)-induced lesions , 2005, Journal of Neural Transmission.

[15]  S. R. Snodgrass,et al.  Effects of adult or neonatal treatment with 6-hydroxydopamine or 5,7-dihydroxytryptamine on locomotor activity, monoamine levels, and response to caffeine , 1986, Pharmacology Biochemistry and Behavior.

[16]  T. Reader,et al.  Review article Effects of denervation and hyperinnervation on dopamine and serotonin systems in the rat neostriatum: implications for human Parkinsons disease , 1999, Neurochemistry International.

[17]  E. Azmitia,et al.  An autoradiographic analysis of the differential ascending projections of the dorsal and median raphe nuclei in the rat , 1978, The Journal of comparative neurology.

[18]  G. Nappi,et al.  Time‐course of nigrostriatal damage, basal ganglia metabolic changes and behavioural alterations following intrastriatal injection of 6‐hydroxydopamine in the rat: new clues from an old model , 2007, The European journal of neuroscience.

[19]  Dopaminergic modulation of serotonin metabolism in rat striatum: a study with dopamine uptake inhibitor GBR-12909. , 1995, Life sciences.

[20]  H. Braak,et al.  Staging of brain pathology related to sporadic Parkinson’s disease , 2003, Neurobiology of Aging.

[21]  M. Hajós,et al.  Evidence for a repetitive (burst) firing pattern in a sub-population of 5-hydroxytryptamine neurons in the dorsal and median raphe nuclei of the rat , 1995, Neuroscience.

[22]  T. Hökfelt,et al.  Chemical anatomy of the brain. , 1984, Science.

[23]  S. Breit,et al.  Bilateral changes in neuronal activity of the basal ganglia in the unilateral 6‐hydroxydopamine rat model , 2008, Journal of neuroscience research.

[24]  G. Mengod,et al.  Control of serotonergic neurons in rat brain by dopaminergic receptors outside the dorsal raphe nucleus , 2001, Journal of neurochemistry.