Local injection of pertussis toxin attenuates morphine withdrawal excitation of rat supraoptic nucleus neurones.
Morphine inhibits oxytocin neurones via G(i/o)-protein-linked mu-opioid receptors. Following chronic morphine administration oxytocin cells develop dependence, shown by withdrawal excitation after administration of the opioid antagonist, naloxone. Here, inactivation of G(i/o)-proteins by pre-treatment of morphine-dependent rats with pertussis toxin injected into the left supraoptic nucleus reduced withdrawal-induced Fos protein expression within the injected nucleus by 41+/-10% compared to the contralateral nucleus, indicating that functional G(i/o)-proteins are essential for the development and/or expression of morphine dependence by oxytocin cells in the supraoptic nucleus. In another group of rats, pertussis toxin did not alter the responses to either systemic cholecystokinin administration or systemic hypertonic saline administration, indicating that pertussis toxin does not prevent oxytocin cells from responding to stimuli that are not mediated by G(i/o)-proteins. Finally, pertussis toxin reduced acute morphine inhibition of systemic hypertonic saline-induced Fos protein expression in the supraoptic nucleus, confirming that pertussis toxin effectively inactivates G(i/o)-proteins in the supraoptic nucleus. Thus, the expression of morphine withdrawal excitation by supraoptic nucleus oxytocin cells requires the functional integrity of G(i/o)-proteins within the nucleus.
Brown
C H
CH
Department of Biomedical Sciences, University Medical School, Edinburgh, UK. Colin.Brown@ed.ac.uk
Johnstone
L E
LE
Murphy
N P
NP
Leng
G
G
Russell
J A
JA
D000818:Animals; D005260:Female; D007839:Functional Laterality; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D020962:Heterotrimeric GTP-Binding Proteins / Q000502:physiology; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D037342:Pertussis Toxin; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D013495:Supraoptic Nucleus / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D010566:Virulence Factors, Bordetella / Q000008:administration & dosage / Q000494:pharmacology*
D016760:Proto-Oncogene Proteins c-fos; D010566:Virulence Factors, Bordetella; D009270:Naloxone; D009020:Morphine; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020962:Heterotrimeric GTP-Binding Proteins; D012844:Sincalide