High frequency stimulation of the subthalamic nucleus increases c-fos immunoreactivity in the dorsal raphe nucleus and afferent brain regions

• Published in: Journal of psychiatric research Vol. 45; no. 10; pp. 1307 - 1315
• Main Authors: Tan, Sonny K.H, Janssen, Marcus L.F, Jahanshahi, Ali, Chouliaras, Leonidas, Visser-Vandewalle, Veerle, Lim, Lee Wei, Steinbusch, Harry W.M, Sharp, Trevor, Temel, Yasin
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-10-2011; Elsevier
• Subjects: Adult and adolescent clinical studies; Afferent Pathways - metabolism; Animals; Biological and medical sciences; Brain - metabolism; Cortex; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Depression; Dorsal raphe nucleus; Electric Stimulation - methods; Gamma-aminobutyric acid; High frequency stimulation; Male; Medical sciences; Mood disorders; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Neurons; Organic mental disorders. Neuropsychology; Parkinson’s disease; Proto-Oncogene Proteins c-fos - metabolism; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Raphe Nuclei - metabolism; Rats; Rats, Inbred Lew; Serotonin; Serotonin (5-HT, 5-Hydroxytryptamine); Stimulation; Subthalamic nucleus; Subthalamic Nucleus - metabolism; Depression; Serotonin (5-HT, 5-Hydroxytryptamine); Subthalamic nucleus; High frequency stimulation; Dorsal raphe nucleus; Parkinson’s disease; Parkinson's disease; Central nervous system; Parkinson disease; Stimulation; Encephalon; Degenerative disease; Protooncogene; Mood disorder; 5-Hydroxytryptamine; Nervous system diseases; Serotonin; fos Gene; Dorsal nucleus; Serotonin 5-HT; Cerebral disorder; Central nervous system disease; Neurotransmitter; Raphe nucleus; High frequency; Extrapyramidal syndrome; Immediate early gene
• ISSN: 0022-3956; 1879-1379
• DOI: 10.1016/j.jpsychires.2011.04.011

Abstract High frequency stimulation (HFS) of the subthalamic nucleus (STN) is the neurosurgical therapy of choice for the management of motor deficits in patients with advanced Parkinson’s disease, but this treatment can elicit disabling mood changes. Our recent experiments show that in rats, HFS of the STN both inhibits the firing of 5-HT (5-hydroxytryptamine; serotonin) neurons in the dorsal raphe nucleus (DRN) and elicits 5-HT-dependent behavioral effects. The neural circuitry underpinning these effects is unknown. Here we investigated in the dopamine-denervated rat the effect of bilateral HFS of the STN on markers of neuronal activity in the DRN as well as DRN input regions. Controls were sham-stimulated rats. HFS of the STN elicited changes in two 5-HT-sensitive behavioral tests. Specifically, HFS increased immobility in the forced swim test and increased interaction in a social interaction task. HFS of the STN at the same stimulation parameters, increased c-fos immunoreactivity in the DRN, and decreased cytochrome C oxidase activity in this region. The increase in c-fos immunoreactivity occurred in DRN neurons immunopositive for the GABA marker parvalbumin. HFS of the STN also increased the number of c-fos immunoreactive cells in the lateral habenula nucleus, medial prefrontal cortex but not significantly in the substantia nigra. Collectively, these findings support a role for circuitry involving DRN GABA neurons, as well as DRN afferents from the lateral habenula nucleus and medial prefrontal cortex, in the mood effects of HFS of the STN.