Galanin Alters GABAergic Neurotransmission in the Dorsal Raphe Nucleus |
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Authors: | Lisa M Sharkey Samuel G Madamba George R Siggins Tamas Bartfai |
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Institution: | (1) Molecular and Integrative Neurosciences Department, The Harold L Dorris Neurological Research Center, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA;(2) Present address: Department of Human Genetics, University of Michigan, 4909 Buhl, Ann Arbor, MI 48109-0618, USA |
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Abstract: | The neuropeptide galanin and its three receptor subtypes (Gal R1-3) are highly expressed in the dorsal raphe nucleus (DRN),
a region of the brain that contains a large population of serotonergic neurons. Galanin is co-expressed with serotonin in
approximately 40% of the DRN neurons, and galanin and GALR2 expression are elevated by antidepressants like the SSRI fluoxetine,
suggesting an interaction between serotonin and galanin. The present study examines the effect of galanin (Gal 1–29), a pan
ligand for GalR (1–3) and the GalR2/GalR3-selective ligand, Gal 2–11, on the electrophysiological properties of DRN serotonergic
neurons in a slice preparation. We recorded from cells in the DRN with electrophysiological characteristics consistent with
those of serotonergic neurons that exhibit high input resistance, large after-hyperpolarizations and long spike duration as
defined by Aghajanian and Vandermaelen. Both Gal 1–29 and Gal 2–11 decreased the amplitudes pharmacologically-isolated GABAergic
inhibitory postsynaptic potentials (IPSPs) in these putative serotonergic neurons. Furthermore, based on paired pulse facilitation
studies, we show that Gal 1–29 likely decreases GABA release through a presynaptic mechanism, whereas Gal 2–11 may act postsynaptically.
These findings may enhance understanding of the cellular mechanisms underlying the effects of antidepressant treatments on
galanin and galanin receptors in DRN.
Special issue article in honor of Dr. Frode Fonnum. |
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Keywords: | Galanin Dorsal raphe nucleus Antidepressant Serotonin GABA |
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