Morphine withdrawal increases expression of GABA(A) receptor epsilon subunit mRNA in locus coeruleus neurons.
An increase in the activity of brain stem locus coeruleus noradrenergic neurons has been hypothesised to be a major factor accounting for opiate withdrawal symptoms. These neurons are under GABAergic inhibition. Their GABA(A) receptors have unique pharmacological properties, most likely due to the enriched expression of GABA(A) receptor subtypes containing novel epsilon and straight theta subunits. Using in situ hybridisation of cryostat sections, we now report a significant increase in the epsilon subunit mRNA expression after precipitation of opioid withdrawal by naloxone. Similar changes were detected in tyrosine hydroxylase mRNA expression. The results suggest increased formation of unique GABA(A) receptor subtype(s) in the locus coeruleus neurons during increased neuronal activity.
Heikkilä
A T
AT
Department of Pharmacology and Clinical Pharmacology, University of Turku, FIN-20520 Turku, Finland.
Echenko
O
O
Uusi-Oukari
M
M
Sinkkonen
S T
ST
Korpi
E R
ER
D000818:Animals; D004347:Drug Interactions / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects* / Q000502:physiology; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D009292:Narcotic Antagonists; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D009270:Naloxone; D005680:gamma-Aminobutyric Acid; D009020:Morphine