High-frequency stimulation of the subthalamic nucleus and L-3,4-dihydroxyphenylalanine inhibit in vivo serotonin release in the prefrontal cortex and hippocampus in a rat model of Parkinson’s disease
Journal of Neuroscience. 2010-02-10; 30(6): 2356-2364
DOI: 10.1523/JNEUROSCI.5031-09.2010
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High-frequency stimulation of the subthalamic nucleus (STN-HFS) and
l-3,4-dihydroxyphenylalanine (l-DOPA) medication are the most used therapeutic
approaches in Parkinson’s disease (PD), but their beneficial motor effects are
burdened by the emergence of cognitive and depressive disorders. Although a
reduced serotonergic function has been linked to the psychiatric effects of
antiparkinsonian treatments, biochemical evidence supporting this hypothesis is
still lacking. By using a microdialysis approach in anesthetized rats, we
investigated the ability of STN-HFS (130 Hz, 30 muA, 20 min) and l-DOPA (6-12
mg/kg) to change extracellular levels of serotonin (5-HT) monitored
simultaneously in the prefrontal cortex (PFC) and hippocampus (HIPP), two brain
regions involved in the regulation of mood and cognition that receive a distinct
5-HT innervation. The results show that STN-HFS inhibited 5-HT levels in the PFC
and HIPP of sham-lesioned and 6-hydroxydopamine (6-OHDA)-lesioned rats. The
effect elicited by STN-HFS was blocked by the administration of the 5-HT(1A)
agonist 8-hydroxy-N,N-dipropyl-2-aminotetralin. l-DOPA (6 and 12 mg/kg) reduced
5-HT levels in the PFC and HIPP of 6-OHDA rats. STN-HFS did not further decrease
5-HT levels induced by l-DOPA, but attenuated l-DOPA-induced dopamine release in
the PFC and HIPP. These neurochemical data show that STN-HFS inhibits 5-HT
release by modulating serotonergic neuron activity, while the decrease in 5-HT
levels induced by l-DOPA may include its direct action inside serotonergic
neurons. These results support the premise that antiparkinsonian treatments
reduce central serotonergic transmission, which may favor the development of
nonmotor side effects in PD.