Verapamil prevents withdrawal excitation of oxytocin neurones in morphine-dependent rats.
We investigated whether the full expression of morphine withdrawal excitation by supraoptic nucleus (SON) oxytocin neurones is a property of the neurones themselves or a partial function of their afferent inputs, by interrupting synaptic input activity via central administration of the L-type Ca(2+) channel blocker verapamil. In morphine-dependent rats, withdrawal-induced release of oxytocin from the posterior pituitary was suppressed by prior administration of intracerebroventricular (i.c.v.) verapamil (160 microg), as was release of oxytocin within the SON measured by microdialysis. During morphine withdrawal the increased electrical activity of SON neurones was also reduced both by i.c.v. verapamil and microdialysis application of verapamil or nifedipine into the SON. Oxytocin secretion evoked by electrical stimulation of the pituitary stalk was unaffected by i.c.v. verapamil suggesting a central site of action. To determine whether the inhibitory actions of verapamil were specific to morphine withdrawal, we also investigated the effects of verapamil on other oxytocin-secreting stimuli. I.C.V. verapamil given to morphine-naïve rats abolished pituitary oxytocin release in response to activation of brainstem or rostral excitatory inputs by cholecystokinin (20 microg kg(-1), i.v.) and 1.5 M saline (4 ml kg(-1), i.p.) respectively, whilst in lactating rats, i.c.v. verapamil reduced suckling-induced release of oxytocin within the SON. These results suggest that verapamil has a central site of action on stimulated oxytocin release (including an action within the SON) and that both pre and post-synaptic L-type Ca(2+) channels are required for the full expression of morphine withdrawal in SON oxytocin neurones.
Blackburn-Munro
G
G
Department of Biomedical Sciences, University Medical School, EH8 9XD, Edinburgh, United Kingdom. gordon.munro@ed.ac.uk
Brown
C H
CH
Neumann
I D
ID
Landgraf
R
R
Russell
J A
JA
D000818:Animals; D000833:Animals, Suckling; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D005260:Female; D006982:Hypertonic Solutions / Q000494:pharmacology; D007276:Injections, Intraventricular; D007774:Lactation; D008564:Membrane Potentials / Q000187:drug effects; D017551:Microdialysis; D009020:Morphine / Q000009:adverse effects; D009021:Morphine Dependence / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000009:adverse effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010121:Oxytocin / Q000187:drug effects / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology / Q000517:prevention & control*; D013388:Succinimides / Q000494:pharmacology; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*
C044758:Bolton Hunter-cholecystokinin octapeptide; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D006982:Hypertonic Solutions; D009292:Narcotic Antagonists; D009294:Narcotics; D013388:Succinimides; D009270:Naloxone; D010121:Oxytocin; D009020:Morphine; D014700:Verapamil; D012844:Sincalide