Effect of chronic exposure to naltrexone and opioid selective agonists on G protein mRNA levels in the rat nervous system.
The in situ hybridization technique was used to investigate the effect on G protein alpha subunit expression throughout the brain of rats chronically infused with naltrexone (70 micrograms/microliters, 1 microliter/h), DAGO (0.5 micrograms/microliter, 1 microliter/h), DADLE (11.4 micrograms/microliters, 1 microliter/h), DPDPE (3.4 micrograms/microliters, 1 microliter/h) and U-50,488H (4 micrograms/microliters, 1 microliter/h). Prolonged exposure to naltrexone did not modify G protein alpha subunit mRNA expression, whereas DADLE and U-50,488H, respectively, increased the levels of alpha s and alpha o mRNA in specific brain regions. In particular, a 15% increase in alpha s expression was only observed in the dorsomedial hypothalamic nucleus of rats undergoing chronic DADLE infusion: a 15% increase in alpha o levels was detected in the claustrum and endopiriform nucleus of rats chronically treated with U-50,488H. These are the first in vivo data to demonstrate that only chronic stimulation with an opioid agonist (morphine and/or DADLE and U-50,488H) is capable of modifying G protein alpha subunit mRNA. The regional selectivity of these modifications is discussed, together with the receptor specificity of the opioid effects.
Rubino
T
T
Institute of Pharmacology, Faculty of Sciences, University of Milan, Italy.
Massi
P
P
Patrini
G
G
Venier
I
I
Giagnoni
G
G
Parolaro
D
D
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004334:Drug Administration Schedule; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D016308:Enkephalin, Leucine-2-Alanine / Q000008:administration & dosage / Q000494:pharmacology; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects*; D017403:In Situ Hybridization / Q000379:methods; D007263:Infusions, Parenteral; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage / Q000494:pharmacology*; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D015345:Oligonucleotide Probes; D009928:Organ Specificity; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004745:Enkephalins; D009294:Narcotics; D015345:Oligonucleotide Probes; D011759:Pyrrolidines; D012333:RNA, Messenger; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D020881:Enkephalin, D-Penicillamine (2,5)-; D019204:GTP-Binding Proteins