Individual contribution of metabotropic glutamate receptor (mGlu) 2 and 3 to c-Fos expression pattern evoked by mGlu2/3 antagonism.
OBJECTIVES AND MATERIALS AND METHODS: The aims of the present study were (1) to determine the neuronal activation pattern elicited by the group II mGlu antagonist LY341495 and (2) to evaluate the contribution of each group II mGlu subtype by using wild-type (WT) and knockout (KO) mice lacking either mGlu2 or mGlu3. c-Fos expression was used as a marker of neuronal activation.


CONCLUSIONS
In WT mice, LY341495 induced widespread c-Fos expression in 68 out of 92 brain areas, including limbic areas such as the amygdala, septum, prefrontal cortex, and hippocampus. LY341495-induced c-Fos response was markedly decreased in the medial part of the central amygdala (CeM) and lateral septum (LS) in mGlu3-KO mice, as well as in the lateral parabrachial nucleus (LPB) in both KO strains. In the majority of investigated areas, LY341495-induced c-Fos expression was similar in KO and WT mice. Analysis of the cellular and subcellular distribution of mGlu2 and mGlu3 revealed a prevailing presence of mGlu3-immunoreactivity in the CeM in glial processes and in postsynapstic neuronal elements, whereas only rare presynaptic axon terminals were found immunoreactive for mGlu2.


CONCLUSIONS
In conclusion, our data indicate that group II mGlu blockade increases neuronal activation in a variety of brain areas, including many stress- and anxiety-related areas. The activation of two key brain areas, the CeM and LS, is mediated via mGlu3, while activation in the LPB involves both subtypes. Moreover, in the majority of investigated areas, LY341495-mediated neuronal activation appears to require a complex cross talk between group II mGlu subtypes or the action of LY341495 on additional receptors.
Hetzenauer
Alfred
A
Department of Pharmacology and Toxicology, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innsbruck, Austria.
Corti
Corrado
C
Herdy
Stefanie
S
Corsi
Mauro
M
Ferraguti
Francesco
F
Singewald
Nicolas
N
D000596:Amino Acids / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D016762:Genes, fos / Q000187:drug effects* / Q000235:genetics* / Q000276:immunology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018094:Receptors, Metabotropic Glutamate / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D020665:Septum of Brain / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D014966:Xanthenes / Q000494:pharmacology
D000596:Amino Acids; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3