Regulation of subthalamic neuron activity by endocannabinoids
Synapse. 2010-01-01; : NA-NA
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1. Synapse. 2010 Sep;64(9):682-98. doi: 10.1002/syn.20778.
Regulation of subthalamic neuron activity by endocannabinoids.
Morera-Herreras T(1), Ruiz-Ortega JA, Taupignon A, Baufreton J, Manuel I,
Rodriguez-Puertas R, Ugedo L.
(1)Department of Pharmacology, Faculty of Medicine, University of the Basque
Country, E-48940 Leioa, Vizcaya, Spain.
High levels of anandamide are located in the basal ganglia. The subthalamic
nucleus (STN) is considered to be an important modulator of basal ganglia output.
The present study aims at characterizing the modulation of the electrical
activity of STN neurons by exogenous anandamide or endocannabinoids. Single-unit
extracellular recordings in anesthetized rats and patch-clamp techniques in rat
brain slices containing the STN were performed. Immunohistochemical assays were
used. In vivo, anandamide administration produced two opposite effects
(inhibition or stimulation) on STN neuron firing rates, depending of the precise
location of the neuron within the nucleus. These effects were enhanced by prior
inhibition of fatty acid amide hydrolase with URB597, but not by the inhibitor of
carrier-mediated anandamide transport AM404. Rimonabant, a specific CB(1)
receptor antagonist, also produced inhibition or stimulation of STN neuron
activity when administered alone or after anandamide. These effects seem to be
mediated by indirect mechanisms since: (1) STN neuron activity is not modified by
the cannabinoid agonist Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in vitro;
(2) no depolarization-induced suppression of inhibition phenomena were observed;
and (3) CB(1) receptor immunolabeling was not detected in the STN, but was
abundant in areas which project efferents to this nucleus. Moreover, chemical
lesion of the globus pallidus abolished the stimulatory effect of anandamide and
microinfusion of anandamide into the prefrontal cortex led to inhibition of STN
neuron activity. The present results show that endocannabinoids exert a tonic
control on STN activity via receptors located outside the nucleus. These findings
may contribute to enhance our understanding of the role of the endocannabinoid
system in motor control.
PMID: 20336631 [Indexed for MEDLINE]