Localization of GABAA receptor subunit mRNAs in the rat locus coeruleus.
Although there is overwhelming evidence for the existence of structurally different subunits of gamma-aminobutyric acid type A (GABAA) receptors in the CNS, the functional relevance of this heterogeneity is not yet known. A first step in this direction is to demonstrate the receptor composition in well characterized transmitter-specific neuronal populations, such as the noradrenergic neurons of the rat locus coeruleus (LC). LC neurons might play a key role in the regulation of vigilance, attention, learning and memory as well as anxiety. In the present investigation we have examined, by in situ hybridization histochemistry, the cellular expression patterns of 13 subunit variants (alpha 1-6, beta 1-3, gamma 1-3 and delta). Identified neurons express mRNAs encoding several GABAA receptor subunits (alpha 3, beta 3 > alpha 2, beta 1 > gamma 1) whereas other transcripts were not detected. These findings suggest that GABAA receptors in the LC are composed of a unique combination of subunits, e.g. alpha 3 beta 3 gamma 1, of unknown stoichiometry. Whether the identification of this potential drug target can be exploited in the development of new anxiolytics or antidepressants remains to be seen.
Pharma Division, Preclinical Research, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
J M
JM
Luque
P
P
Malherbe
J G
JG
Richards
D000818:Animals; D015870:Gene Expression; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008125:Locus Coeruleus / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male; D009474:Neurons / Q000378:metabolism*; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000032:analysis* / Q000096:biosynthesis; D051381:Rats; D011963:Receptors, GABA-A / Q000032:analysis / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000096:biosynthesis
D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D014446:Tyrosine 3-Monooxygenase