Enhanced hippocampal noradrenaline and serotonin release in galanin-overexpressing mice after repeated forced swimming test.
Basal and forced swimming (FS) stress-induced release of noradrenaline (NA) and serotonin (5-HT) were determined by in vivo microdialysis in the ventral hippocampus of mice overexpressing galanin under the platelet-derived growth factor B promoter (GalOE/P) or under the dopamine beta-hydroxylase promoter (GalOE/D) (only NA). WT mice served as controls. Intraventricular infusion of galanin significantly reduced basal extracellular NA in WT mice and in GalOE/P mice (albeit less so). Microdialysis sampling during a 10-min FS showed that NA and 5-HT release were elevated to 213% and 156%, respectively, in the GalOE/P group, whereas in the WT group the increases were only 127% and 119%, respectively. The second (repeated) 10-min FS (RFS) caused a marked enhancement of NA and 5-HT release in the GalOE/P mice to 344% and 275%, respectively. However, the RFS caused only a 192% increase of extracellular NA levels in the GalOE/D mice. Pretreatment with the putative peptidergic galanin receptor antagonist M35 almost completely blocked the elevation of NA and 5-HT levels in the GalOE/P after RFS. These results suggest that the NA and 5-HT hippocampal afferents in GalOE/P mice are hypersensitive to both conditioned and unconditioned stressful stimuli, such as FS, and that this effect is mediated by galanin receptors. The present findings support a role of galanin in the regulation of release of NA and 5-HT, two neurotransmitters involved in mood control.
Yoshitake
Takashi
T
Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 171 77 Stockholm, Sweden.
Wang
Fu-Hua
FH
Kuteeva
Eugenia
E
Holmberg
Kristina
K
Yamaguchi
Masatoshi
M
Crawley
Jacqueline N
JN
Steiner
Robert
R
Bartfai
Tamas
T
Ogren
Sven Ove
SO
Hökfelt
Tomas
T
Kehr
Jan
J
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D005260:Female; D019004:Galanin / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology*; D015870:Gene Expression; D020571:Genes, sis; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000494:pharmacology; D005082:Physical Exertion / Q000502:physiology*; D011401:Promoter Regions, Genetic; D044088:Receptors, Galanin / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000378:metabolism*; D013550:Swimming / Q000502:physiology
D010446:Peptide Fragments; D044088:Receptors, Galanin; C074069:galanin-(1-13)-bradykinin-(2-9)-amide; D012701:Serotonin; D019004:Galanin; D004299:Dopamine beta-Hydroxylase; D001920:Bradykinin