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Modulation of the Subthalamic Nucleus Activity by Serotonergic Agents and Fluoxetine Administration

Modulation of the Subthalamic Nucleus Activity by Serotonergic Agents and Fluoxetine Administration

A Aristieta, T Morera-Herreras, J A Ruiz-Ortega, C Miguelez, I Vidaurrazaga, A Arrue, M Zumarraga, L Ugedo

Psychopharmacology (Berl). 2014 May;231(9):1913-24.

PMID: 24271033

Abstract:

Rationale:
Within the basal ganglia, the subthalamic nucleus (STN) is the only glutamatergic structure and occupies a central position in the indirect pathway. In rat, the STN receives serotonergic input from the dorsal raphe nucleus and expresses serotonergic receptors.
Objective:
This study examined the consequences of serotonergic neurotransmission modulation on STN neuron activity.
Methods:
In vivo single-unit extracellular recordings, HPLC determination, and rotarod and bar test were performed in control, 4-chloro-DL-phenylalanine methyl ester hydrochloride- (pCPA, a serotonin synthesis inhibitor) and chronically fluoxetine-treated rats.
Results:
The pCPA treatment and the administration of serotonin (5-HT) receptor antagonists increased number of bursting neurons in the STN. The systemic administration of the 5-HT(1A) agonist, 8-OH-DPAT, decreased the firing rate and increased the coefficient of variation of STN neurons in pCPA-treated rats but not in control animals. Additionally, microinjection of 8-OH-DPAT into the STN reduced the firing rate of STN neurons, while microinjection of the 5-HT(2C) agonist, Ro 60-0175, increased the firing rate in both control and fluoxetine-treated animals. Finally, the fluoxetine challenge increased the firing rate of STN neurons in fluoxetine-treated rats and induced catalepsy.
Conclusions:
Our results indicate that the depletion and the blockage of 5-HT modify STN neuron firing pattern. STN neuron activity is under the control of 5-HT(1A) and 5-HT(2C) receptors located both inside and outside the STN. Finally, fluoxetine increases STN neuron activity in chronically fluoxetine-treated rats, which may explain the role of this nucleus in fluoxetine-induced extrapyramidal side effects.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP14173401	4-Chloro-DL-phenylalanine methyl ester hydrochloride		14173-40-1	Price

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