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

Abstract

Objective - To measure oxytocin concentrations in blood and CSF following central administration of opioid agonists in dogs. Animals - 5 male dogs. Procedure - In a crossover design, CSF and blood were collected immediately before and 15 and 30 minutes after cisternal administration of D-Ala2, MePhe4, Gly-ol-enkephalin (DAMGO, a μ-receptor agonist); D-Pen, pCl-Phe4, D-Pen5-enkephalin (a δ-receptor agonist); U50488H (a κ-receptor agonist); morphine; and saline (0.9% NaCl) solution. Results - Plasma oxytocin concentration was significantly increased 15 minutes after administration of DAMGO and 30 minutes after administration of U50488H, compared with concentrations obtained after administration of saline solution. Concentration of oxytocin in CSF was significantly decreased 30 minutes after administration of U50488H, compared with concentration after administration of saline solution. Conclusions and Clinical Relevance - Results suggest that in male dogs, activation of centrally located μ and κ receptors elicits an overall excitatory effect on neurons that regulate peripheral release of oxytocin, whereas activation of centrally located κ receptors elicits an overall inhibitory effect on neurons that regulate central release. These results are in contrast to those reported for other species, in which opioids have a pronounced inhibitory effect on release of oxytocin from the neurohypophysis.