The role of endogenous opioids in the stress- and estrogen-induced activation of prolactin release.

Previously, we demonstrated that morphine (MOR) and opioid peptides inhibit the turnover of dopamine (DA) in the tuberoinfundibular pathway (TIP) in a dose-dependent, naloxone (NAL)-reversible manner. Subsequent studies showed that tolerance to both the effects of MOR on PRL release and DA turnover in the median eminence (ME) develops during the same period of chronic MOR treatment, which supports the idea that opioids increase the rate of PRL release by inhibiting the activity of the DA neurons of the TIP, which inhibit the release of PRL. We now report that cross-tolerance develops between the effects of ether stress and MOR on plasma PRL levels, which strongly supports the idea that endogenous opioids are involved in the stress-induced activation of PRL release. However, our data do not support the idea that opioid pathways are involved in the estrogen-induced activation of PRL release. The evidence against opioid mediation of estrogen's action on the release of PRL follows. 1.) The effects of 17-beta-estradiol (EB) and of a maximally effective dose of MOR on plasma PRL concentration are additive, which suggests that these agents act by different mechanisms. 2.) EB increases the rate of DA turnover in the ME of ovariectomized (OVX) rats treated for 3 days with 20 micrograms/kg of EB per day, while MOR inhibits DA turnover in this group and all other groups studied. 3.) Although NAL decreases EB-elevated plasma PRL levels at one of two time points that were studied, it also inhibits the effect of alpha-methyl-rho-tyrosine (AMT) on the concentration of PRL in the plasma, and AMT acts by a non-opioid mediated mechanism to activate the release of PRL.