Effects of metabotropic glutamate 2/3 receptor antagonists in the stress-induced hyperthermia test in singly housed mice.
BACKGROUND
The stress-induced hyperthermia (SIH) test in mice has been widely used as models including some physiological aspects of psychiatric disorders. Mediated by the autonomic nervous system, SIH is commonly known to occur both before and during exposure to stress-inducing or anxiogenic situations. Recently, modulation of the group II metabotropic glutamate (mGlu) 2/3 receptor has been proposed as a novel therapeutic approach for psychiatric disorders.


OBJECTIVE
In the present study, we evaluated the efficacy of selective mGlu2/3 receptor antagonists and an mGlu2/3 receptor agonist in the SIH test.


RESULTS
mGlu2/3 receptor antagonists such as MGS0039 and LY341495 significantly and dose-dependently reduced SIH without affecting basal rectal temperatures. In contrast, mGlu2/3 receptor agonists such as MGS0008 were ineffective in the SIH test. The attenuation of SIH by MGS0039 was significantly blocked by pretreatment with WAY100635, a serotonin 1A receptor antagonist. In contrast, an AMPA receptor potentiator, CX546 failed to reduce the SIH.


CONCLUSIONS
Taken together, these results suggest that the blockade of mGlu2/3 receptor may prevent stress-induced autonomic hyperactivity, and that stimulation of the postsynaptic serotonin 1A receptor, but not AMPA receptor, may be involved in this action.
Iijima
Michihiko
M
Psychiatric Diseases and Pain Research, Medicinal Pharmacology Laboratory, Medicinal Research Laboratories, Taisho Pharmaceutical Co Ltd, Saitama, Japan.
Shimazaki
Toshiharu
T
Ito
Akie
A
Chaki
Shigeyuki
S
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology*; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology*; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D012934:Social Isolation; D014966:Xanthenes / Q000494:pharmacology
C483757:2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo(3.1.0)hexane-2,6-dicarboxylic acid; D000596:Amino Acids; D001643:Bridged Bicyclo Compounds; D003998:Dicarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D010879:Piperazines; D011725:Pyridines; D018094:Receptors, Metabotropic Glutamate; D012702:Serotonin Antagonists; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide