Regionally selective effects of GABA on hypothalamic GABAA receptor mRNA in vitro.
We tested whether GABAA receptor (R) subunit mRNA levels are homeostatically influenced by short-term exposure to GABA in two adjacent regions of the posterior hypothalamus. mRNA levels for seven GABAAR subunits and GABA-synthesizing enzyme (GAD) were quantified in the perifornical (PF) and dorsomedial (DM) hypothalamus following superfusion of slices for 90 min with a drug-free medium, GABA uptake blocker with or without GABAAR antagonist, gabazine, or GABAAR agonist with tetrodotoxin. Increasing endogenous GABA decreased mRNAs for all seven GABAAR subunits in the PF, and for three also in the DM, region; gabazine antagonized these effects in the PF region only and increased GAD-65 mRNA. Stimulation of GABAARs in the presence of tetrodotoxin decreased mRNA for one GABAAR subunit (beta1). We conclude that, in the PF region where GABA facilitates sleep, increased GABA release may limit GABAAR-mediated inhibition, whereas in the DM region, GABA-induced changes are mainly mediated by non-GABAA receptors.
Volgin
Denys V
DV
Department of Animal Biology, School of Veterinary Medicine and Center for Sleep and Respiratory Neurobiology, University of Pennsylvania, Philadelphia, PA 19104-6046, USA. dvolgin@vet.upenn.edu
Kubin
Leszek
L
D000818:Animals; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009557:Nipecotic Acids / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000235:genetics*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D007527:Isoenzymes; D009557:Nipecotic Acids; D010091:Oximes; D011724:Pyridazines; D012333:RNA, Messenger; D011963:Receptors, GABA-A; C078793:NNC 711; D009118:Muscimol; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; C049853:gabazine; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2