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Abstract
The release of the nonapeptides oxytocin and vasopressin within the hypothalamic supraoptic
and paraventricular nuclei was measured in 30-min microdialysates in conscious female
rats in the last three days of pregnancy, during parturition, immediately after parturition
and during suckling, all in the same rats, and in virgin controls. Nonapeptide release
within the supraoptic and paraventricular nuclei was unchanged during late pregnancy
compared to virgin rats, but intranuclear oxytocin and not vasopressin release was
elevated during parturition (relative to late pregnancy, supraoptic nucleus: to 254%,
paraventricular nucleus: to 300%; P < 0.01) and during suckling also on days 8-10
of lactation (relative to pre-suckling, supraoptic nucleus: to 407%, paraventricular
nucleus: to 275%; P < 0.02). Suckling-induced release of oxytocin was significantly
reduced using Ca(2+)-free, EDTA-containing (10(-4) M) microdialysis fluid and further
stimulated by high K(+)- (56 mM), veratridine-containing (50 microM) microdialysis
fluid. The opioid antagonist naloxone whether given by subcutaneous injection (5 mg/kg)
or directly into the supraoptic nucleus by microdialysis (5 x 10(-6) M) or microinjection
(1.5 microliters, 10(-6) M) did not further enhance oxytocin release within either
the supraoptic or paraventricular nuclei during parturition. In contrast to the selective
release of oxytocin within the supraoptic and paraventricular nuclei during parturition
and suckling, direct osmotic stimulation of the nuclei by microdialysing hypertonic
medium (artificial cerebrospinal fluid; 1 M NaCl) increased intranuclear release of
both oxytocin and vasopressin which was further enhanced after replacement of hypertonic
with isotonic fluid. This rebound phenomenon served to confirm the precise location
of the microdialysis probe ante mortem and the ability of the nuclei to adequately
respond to the osmotic stimulus at the end of the experiment. The study has shown
that oxytocin is released in the supraoptic and paraventricular nuclei during parturition
as well as in lactation unrestrained by endogenous opioids during parturition. This
intranuclear release of oxytocin may act by local positive feedback stimulation of
oxytocin neurons to excite further oxytocin release in the brain and into blood during
both parturition and lactation.