Galanin Is a Potent In Vivo Modulator of Mesencephalic Serotonergic Neurotransmission

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 27; no. 3; pp. 341 - 356
• Main Authors: Kehr, Jan, Yoshitake, Takashi, Wang, Fu-Hua, Razani, Haleh, Gimenez-Llort, Lydia, Jansson, Anders, Yamaguchi, Masatoshi, Ögren, Sven Ove
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2002; Nature Publishing; Nature Publishing Group
• Subjects: 5-HT1A Receptors; 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; Analysis of Variance; Animals; Binding sites; Biological and medical sciences; Body Temperature - drug effects; Bradykinin - analogs & derivatives; Bradykinin - pharmacology; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dorsal raphe nucleus; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Galanin; Galanin - pharmacology; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Immunohistochemistry; In Situ Hybridization; Locomotor activity; Male; Medical sciences; Medicin och hälsovetenskap; Mesencephalon - cytology; Mesencephalon - drug effects; Mesencephalon - physiology; Microdialysis; Motor Activity - drug effects; Neuropharmacology; Neurosciences; Neurotransmitters. Neurotransmission. Receptors; Peptide Fragments - pharmacology; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Receptors, Serotonin - drug effects; Receptors, Serotonin - physiology; Receptors, Serotonin, 5-HT1; Serotonin; Serotonin - secretion; Serotoninergic system; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Tryptophan Hydroxylase - biosynthesis; Tryptophan Hydroxylase - drug effects; Tryptophan Hydroxylase - genetics; Vertebrates: nervous system and sense organs; Sweden; 5-HT1A Receptors; Microdialysis; Galanin; Serotonin; Dorsal raphe nucleus; Hippocampus; Locomotor activity; Serotoninergic transmission; Rat; Galanin receptor; Peptide hormone; Central nervous system; Neuropeptide; 5-HT1A Serotonine receptor; Antagonist; Enzyme; Rodentia; Endogenous substance; Gene expression; Biological activity; Hypothalamic hormone; Locomotion; Vertebrata; Mammalia; Tryptophan 5-monooxygenase; Animal; Intracerebral administration; Raphe nucleus; Oxidoreductases; Brain (vertebrata)
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1016/S0893-133X(02)00309-3

Neurochemical, molecular, immunohistochemical and behavioral methods were used to examine the in vivo effects of the neuropeptide galanin on central 5-HT neurotransmission and on 5-HT1A receptor-mediated responses. Intraventricularly infused galanin caused a long-lasting and dose-dependent reduction of basal extracellular 5-HT levels in the ventral hippocampus of awake rats as measured by microdialysis. Infusion of galanin into the dorsal raphe nucleus (DRN), but not intra-hippocampally, reduced 5-HT release. The effect of i.c.v. galanin on 5-HT release was blocked by the galanin receptor antagonist M35, acting most likely via galanin receptors at the level of the DRN. Galanin also reduced the levels of tryptophanhydroxylase mRNA in the DRN. Therefore, the effects of galanin on 5-HT1A receptor-mediated responses were further investigated. Surprisingly, galanin significantly attenuated the reduction of hippocampal 5-HT release induced by systemic injection of the 5-HT1A receptor agonist 8-OH-DPAT. Galanin also attenuated 8-OH-DPAT-induced hypothermia and locomotor activity in rats. These results indicate that galanin has important inhibitory actions on central 5-HT neurotransmission and on 5-HT1A receptor-mediated events.