Previous studies in this laboratory have indicated that during pregnancy there is an activation of opioid-containing systems. One overall objective is to determine those parameters of the opioid system (anatomical and neurochemical) the modulation of which are involved in this activation and the concomitant increase in maternal pain threshold. The specific objectives are to (1) Determine the effects of hypophysectomy (on day 12 of pregnancy) alone and together with dexamethasone or ACTH replacement therapy on the naltrexone-reversible increase in flinch-jump threshold observed during pregnancy. (2) Determine the effect of adrenalectomy alone and together with dexamethasone and corticosterone administration on flinch-jump threshold in the pregnant rat. (3) Determine the concentration profile of B-endorphin and total opioid activity in maternal blood and placenta. The effects of the above procedures on plasma opioid activity will also be investigated. (4) Determine the relative involvement of spinal and supraspinal opioid mechanisms in pregnancy-induced analgesia. The opioid activity in spinal and ventricular CSF will be determined and compared for pregnant and nonpregnant rats. The involvement of increased hypogastric nerve activity to activate spinal and/or supraspinal opioid mechanisms will also be studied. (5) Determine whether there is any modulation of central maternal opiate receptors (affinity, density, GTP sensitivity) during gestation. Changes in the above binding parameters of the various subtypes of opioid receptor (u, Delta, k) will be analyzed by using radiolabeled ligands of known receptor subtype specificity. In addition to analyzing the binding characteristics of opiate receptors in homogenates of whole brain (minus the cerebellum), binding studies will also be performed on discrete brain regions in order to make possible the detection of a localized receptor modulation. A second overall objective is to study the effects on other brain neuronal systems of modulating one of the parameters that determine the level of opioid activity, receptor number. The specific objective will be to (6) Determine the effect of antagonist-induced or pragnancy-induced increase in opiate receptor density on the turnover rate of the biogenic monoamine neurotransmitters, dopamine, norepinephrine and serotonin in discrete brain areas.
