Oscillations of gene expression and physiological activity in suprachiasmatic nucleus (SCN) neurons result from autoregulatory feedback loops of circadian clock gene transcription factors. In the present experiment, we have determined the pattern of PERIOD1 (PER1), PERIOD2 (PER2), and CLOCK expression within neuroendocrine dopaminergic (DAergic) neurons (NDNs) of ovariectomized (OVX) rats. We have also determined the effects of per1, per2, and clock mRNA knockdown in the SCN with antisense deoxyoligonucleotides (AS-ODN) on DA release from NDNs. Diurnal rhythms of PER1 and PER2 expression in tuberoinfundibular DAergic (TIDA) and periventricular hypophyseal DAergic (PHDA) neurons, peaked at circadian time (CT)18 and CT12, respectively. Rhythms of PER1 expression in tuberhypophyseal neuroendocrine DAergic (THDA) neurons were undetectable. Rhythms of PER2 expression were found in all three populations of NDNs, with greater levels of PER2 expression between CT6 and CT12. AS-ODN injections differentially affected DA turnover in the axon terminals of the median eminence (ME), neural lobe (NL) and intermediate lobe (IL) of the pituitary gland, resulting in a significant decrease in DA release in the early subjective night in the ME (TIDA), a significant increase in DA release at the beginning of the day in the IL (PHDA), and no effect in the NL (THDA). AS-ODN-treatment induced a rhythm of DA concentration in the anterior lobe, with greater DA levels in the middle of the day. These data suggest that clock gene expression, particularly PER1 and PER2, within NDNs may act to modulate diurnal rhythms of DA release from NDNs in the OVX rat.prolactin; dopamine; suprachiasmatic nucleus; hypothalamus DOPAMINE (DA) of hypothalamic origin exerts tonic inhibitory control over prolactin (PRL) secretion (for review see Ref. 17). DA is released directly into hypothalamo-hypophyseal portal blood from three populations of neuroendocrine DAergic neurons (NDNs) (5, 17). These subpopulations include the tuberoinfundibular DAergic (TIDA) and tuberohypophyseal neuroendocrine DAergic (THDA,A12) neurons with cell bodies in the arcuate nucleus (ARN) and periventricular hypophyseal DAergic (PHDA,A14) neurons with cell bodies in the periventricular region (5, 17). THDA and PHDA axons traverse the pituitary stalk and terminate on fenestrated short portal vessels within the neural (NL) and intermediate (IL) lobes of the pituitary gland (21). TIDA axons terminate on fenestrated capillary beds within the external zone of the median eminence (ME) that drain into long portal vessels, transporting DA to the anterior lobe (AL) of the pituitary gland (8, 10). TIDA neurons are well established as the primary PRL inhibitory neurons, although growing importance has been assigned to both THDA and PHDA neurons in the regulation of PRL secretion (13, 21, 43, 52, 61).We have observed diurnal rhythms of DA turnover in the nerve terminals of TIDA, THDA, and PHDA neurons in the ovariectomized (OVX) rat (57, 58). Whereas both TIDA and PHDA neurons display circadian ...