title: Galanin subtype 1 and subtype 2 receptors mediate opposite anxiety-like effects in the rat dorsal raphe nucleus.
abstract: About 40% of the dorsal raphe nucleus (DRN) neurons co-express serotonin (5-HT) and galanin. Serotonergic pathways from the DRN to the amygdala facilitate learned anxiety, while those from the DRN to the dorsal periaqueductal grey matter (DPAG) impair innate anxiety. Previously, we showed that galanin infusion in the DRN of rats induces anxiolytic effect by impairing inhibitory avoidance without changing escape behaviour in the elevated T-maze (ETM). Here, we evaluated: (1) which galanin receptors would be involved in the anxiolytic effect of galanin in the DRN of rats tested in the ETM; (2) the effects of galanin intra-DRN on panic-like behaviours evoked by electrical stimulation of the DPAG. The activation of DRN GAL1 receptors by M617 (1.0 and 3.0nmol) facilitated inhibitory avoidance, whereas the activation of GAL2 receptors by AR-M1896 (3.0nmol) impaired the inhibitory avoidance in the ETM, suggesting an anxiogenic and an anxiolytic-like effect respectively. Both agonists did not change escape behaviour in the ETM or locomotor activity in the open field. The anxiolytic effect of AR-M1896 was attenuated by the prior administration of WAY100635 (0.18nmol), a 5-HT1A antagonist. Galanin (0.3nmol) administered in the DRN increased discreetly flight behaviours induced by electrical stimulation of the DPAG, suggesting a panicolytic effect. Together, our results showed that galanin mediates opposite anxiety responses in the DRN by activation of GAL1 and GAL2 receptors. The anxiolytic effect induced by activation of Gal2 receptors may depend on serotonergic tone. Finally, the role of galanin in panic related behaviours remains uncertain.
authors: Biochemistry and Pharmacology Graduation Program, Federal University of Espirito Santo, Brazil.
authors: J S
authors: JS
authors: Morais
authors: Department of Pharmaceutical Sciences, Health Science Center, Federal University of Espirito Santo, Brazil.
authors: M M
authors: MM
authors: Souza
authors: Department of Pharmaceutical Sciences, Health Science Center, Federal University of Espirito Santo, Brazil.
authors: T M N
authors: TM
authors: Campanha
authors: Physiological Sciences Graduation Program, Federal University of Espirito Santo, Brazil.
authors: C J T
authors: CJ
authors: Muller
authors: Biochemistry and Pharmacology Graduation Program, Federal University of Espirito Santo, Brazil.
authors: A S
authors: AS
authors: Bittencourt
authors: Biochemistry and Pharmacology Graduation Program, Federal University of Espirito Santo, Brazil.
authors: V C
authors: VC
authors: Bortoli
authors: Biochemistry and Pharmacology Graduation Program, Federal University of Espirito Santo, Brazil; Physiological Sciences Graduation Program, Federal University of Espirito Santo, Brazil.
authors: L C
authors: LC
authors: Schenberg
authors: Biochemistry and Pharmacology Graduation Program, Federal University of Espirito Santo, Brazil; Department of Pharmaceutical Sciences, Health Science Center, Federal University of Espirito Santo, Brazil. Electronic address: vanessabh77@gmail.com.
authors: V
authors: V
authors: Beijamini
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism; D001008:Anxiety Disorders / Q000188:drug therapy; D065847:Dorsal Raphe Nucleus / Q000187:drug effects* / Q000378:metabolism; D019004:Galanin / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D010487:Periaqueductal Gray / Q000187:drug effects; D017208:Rats, Wistar; D044091:Receptor, Galanin, Type 1 / Q000187:drug effects* / Q000378:metabolism; D044092:Receptor, Galanin, Type 2 / Q000187:drug effects* / Q000378:metabolism; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology
chemical_list: D014151:Anti-Anxiety Agents; D044091:Receptor, Galanin, Type 1; D044092:Receptor, Galanin, Type 2; D058829:Serotonin 5-HT1 Receptor Antagonists; D019004:Galanin
keywords: 5-HT; Anxiety; Dorsal raphe nucleus; GAL(1); GAL(2); Galanin