Dopamine transporters participate in the physiological regulation of prolactin

Three populations of hypothalamic neuroendocrine dopaminergic (NEDA) neuron s, arising from the arcuate and periventricular nuclei of the hypothalamus release dopamine (DA) that acts at the pituitary gland to regulate the secr etion of PRL. It is generally accepted that NEDA neurons lack functional DA transporters (DATs), which are responsible for uptake of DA from the synap tic cleft into the presynaptic axon terminal. This study localized DATs to the hypothalamopituitary axis and evaluated the effect of DAT blockade on t he hypothalamo-pituitary regulation of PRL. After 7 days of treatment with cocaine (a nonspecific amine transporter blocker) or mazindol(a specific DA T blocker), the relative abundance of PRL messenger RNA (mRNA) in the anter ior lobe (AL) of OVX rats was significantly decreased, whereas the relative abundance of tyrosine hydroxylase mRNA in the hypothalamus was significant ly increased. The effect of cocaine or mazindol administration on DA turnov er and serum PRL concentration was examined in estradiol (E-2)- treated OVX rats. E-2 administration (iv) resulted in a significant increase in serum PRL within 4 h; however, cocaine or mazindol administration abolished the E -2-induced increase of PRL. Cocaine or mazindol significantly increased the concentration of DA at the site of the axon terminals within the median em inence (ME), intermediate lobe (IL) and neural lobe (NL), indicating blocka de of uptake. Because formation of DOPAC requires uptake of DA, concentrati ons of DOPAC in the ME, IL and NL decreased following treatment with either cocaine or mazindol. These data, together with the presence of immunoposit ive DAT in the ME, pituitary stalk, IL, and NL, suggest that a functional D AT system is present within all three populations of NEDA neurons. Moreover , similarity between the effects of cocaine and mazindol treatment indicate that blockade of the DAT, but not other amine transporters, is responsible for suppression of PRL gene expression and secretion. Blockade of DATs pre vent uptake of DA into NEDA neurons and consequently increases the amount o f DA that diffuses into the portal vasculature and reaches the AL. These da ta provide evidence that DATs play a physiological role in the regulation o f DA release from and TH expression in NEDA neurons and consequently PRL se cretion and PRL gene expression and further support our previous observatio n that the regulation of PRL secretion involves all three populations of NE DA neurons.