title: Enhanced serotonin response in the hippocampus of Galphaz protein knock-out mice.
abstract: The serotonin-1A [5-hydroxytryptamine 1A (5HT1A)] receptor is important for emotional and homeostatic processes in the central nervous system. In the hippocampus, the 5HT1A receptor couples to inhibitory Gi/o proteins to decrease pyramidal cell excitability. Here we investigate the 5HT1A receptor in a mouse deficient in the alpha-subunit of Gz protein (Galphaz knock-out). Behavioural tests showed heightened anxiety and depression-like behaviour in the Galphaz knock-out mice. Whole-cell recording in CA1 pyramidal neurons showed a significantly greater 5HT1A receptor-mediated potassium current in Galphaz knock-out mice. The effect was independent of 5HT4 receptors as the slow after-hyperpolarization was unaffected and a slow depolarization was absent in the Galphaz knock-out mice. Other receptors linked to Gi/o proteins [gamma-aminobutyric acid type B receptor (GABAB), adenosine A1 and muscarinic acetylcholine receptors] were not affected in Galphaz knock-out mice. These results suggest that the 5HT1A receptor may be linked to Galphaz protein, as reported previously in cell culture but shown here in an intact neural network.
authors.affiliation: Garvan Institute of Medical Research, Sydney, Australia. S.Oleskevich@garvan.org.au
authors.forename: Sharon
authors.initials: S
authors.lastname: Oleskevich
authors.forename: Kwong-Joo
authors.initials: KJ
authors.lastname: Leck
authors.forename: Klaus
authors.initials: K
authors.lastname: Matthaei
authors.forename: Ian A
authors.initials: IA
authors.lastname: Hendry
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001522:Behavior, Animal / Q000502:physiology; D015153:Blotting, Western / Q000379:methods; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004347:Drug Interactions; D004553:Electric Conductivity; D004558:Electric Stimulation / Q000379:methods; D005455:Fluorescent Antibody Technique / Q000379:methods; D018755:GABA Agonists / Q000494:pharmacology; D044385:GTP-Binding Protein alpha Subunits / Q000172:deficiency* / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D010879:Piperazines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013550:Swimming / Q000502:physiology
chemical_list: D018679:Cholinergic Agonists; D018755:GABA Agonists; D044385:GTP-Binding Protein alpha Subunits; C490964:Gnaz protein, mouse; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D002217:Carbachol; D001418:Baclofen; D000241:Adenosine; D011188:Potassium