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Galanin Alters GABAergic Neurotransmission in the Dorsal Raphe Nucleus

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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.

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Acknowledgments

We thank Drs. Marisa Roberto, Paul Schweitzer for helpful comments on the manuscript, and Novartis Pharma AG for the gift of CGP 55845A. This work has been supported by grants from NIMH to TB and from NIDA to GRS, respectively.

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  1. Lisa M. Sharkey

    Present address: Department of Human Genetics, University of Michigan, 4909 Buhl, Ann Arbor, MI, 48109-0618, USA

Authors and Affiliations

  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

    Lisa M. Sharkey, Samuel G. Madamba, George R. Siggins & Tamas Bartfai

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  1. Lisa M. Sharkey
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  2. Samuel G. Madamba
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  3. George R. Siggins
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  4. Tamas Bartfai
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Correspondence to Lisa M. Sharkey.

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Special issue article in honor of Dr. Frode Fonnum.

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Sharkey, L.M., Madamba, S.G., Siggins, G.R. et al. Galanin Alters GABAergic Neurotransmission in the Dorsal Raphe Nucleus. Neurochem Res 33, 285–291 (2008). https://doi.org/10.1007/s11064-007-9524-5

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  • DOI: https://doi.org/10.1007/s11064-007-9524-5

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