Effect of centrally administered opioid receptor agonists on CSF and plasma oxytocin concentrations in dogs

Objective-To measure oxytocin concentrations in blood and CSF following cen tral administration of opioid agonists in dogs. Animals-5 male dogs. Procedure-In a crossover design, CSF and blood were collected immediately b efore and 15 and 30 minutes after cisternal administration of D-Ala(2), MeP he4, Gly-ol-enkephalin (DAMGO, a mu -receptor agonist); D-Pen, pCI-Phe(4), D-Pen(5)-enkephalin (a delta- receptor agonisti; U50488H (a kappa -receptor agonist); morphine; and saline 10.9% NaCl) solution. Results-Plasma oxytocin concentration was significantly increased 15 minute s after administration of DAMGO and 30 minutes after administration of U504 88H, compared with concentrations obtained after administration of saline s olution. Concentration of oxytocin in CSF was significantly decreased 30 mi nutes after administration of U50488H, compared with concentration after ad ministration of saline solution. Conclusions and Clinical Relevance-Results suggest that in male dogs, activ ation of centrally located mu and kappa receptors elicits an overall excita tory effect on neurons that regulate peripheral release of oxytocin, wherea s activation of centrally located kappa receptors elicits an overall inhibi tory effect on neurons that regulate central release. These results are in contrast to those reported for other species, in which opioids have a prono unced inhibitory effect on release of oxytocin from the neurohypophysis.