Enhanced serotonin response in the hippocampus of Galphaz protein knock-out mice.
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.
Oleskevich
Sharon
S
Garvan Institute of Medical Research, Sydney, Australia. S.Oleskevich@garvan.org.au
Leck
Kwong-Joo
KJ
Matthaei
Klaus
K
Hendry
Ian A
IA
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
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