Sympathetic innervation of mammary glands mediates suckling-induced reflex inhibition of milk yield in rats Teresa Morales, Edna Shapiro, Nephtalı ´ Marina, Flavio Mena* Centro de Neurobiologı ´a, Universidad Nacional Auto ´noma de Me ´xico, Campus UNAM, Apdo. Postal 1-1141 76230 Juriquilla, Quere ´taro, Qro., Me ´xico Received 30 November 2000; received in revised form 22 March 2001; accepted 24 April 2001 Abstract Previous work has shown that physiologic activation of the sympathetic system may inhibit milk yield (ME) in rats. Thus, adrenal catecholamines (CAs) are released by suckling, but it is not known whether such inhibition results also from reflex activation by the same stimulus of neural sympathetics upon the mammary gland. The present experiments were designed to determine whether suckling inhibits ME induced by oxytocin (OT) in the urethane-anesthetized lactating rat, and whether such inhibition results from adrenal and/or neurally released CAs. Rats were isolated (6 h) from their pups and then anesthetized. OT (0.8 mU every 2 min) was administered intravenously to the mothers during suckling. Rats were either chronically implanted with cannulae into the lateral cerebral ventricles (intracerebroventricularly), bilaterally adrenalectomized (ADX), hypophysectomized (HX), spinal cord transected (SCT: T3 –T4), or had the nipple area (NA) locally anesthetized before suckling. MEs were low in control, sham, ADX and HX rats, but not in rats given the b-adrenergic blocker propranolol (PROP; intravenously or intracerebroventricularly injected), nor in SCT, NA or PROP-HX rats. As revealed by ductal resistance measurements as an indicator of ductal tone, suckling-induced inhibition of ME was due to ductal constriction within the mammary glands. These effects of suckling, however, could be prevented by prior activation of ductal mechanoreceptors. Together, these results indicate that suckling inhibits ME through the reflex activation of neurally mediated central b-adrenergic mechanisms, and that these effects, in turn, can be regulated by ductal mechanoreceptor activation. D 2001 Elsevier Science Inc. All rights reserved. Keywords: Mammary gland; Sympathetic innervation; Lactation; Milk yield 1. Introduction Neuroendocrine regulation of milk yield (ME) in rats and other species involves activation by suckling of ant- agonistic mechanisms, which interact at different levels. Thus, the suckling-evoked release of CAs [2,3,6,10,16] may inhibit the release of oxytocin (OT) [29]. In turn, circulating CAs may counteract the milk ejecting action of OT by ductal constriction within the mammary glands [11,13] and through competitive antagonism with OT at the myoepithelial cells [4,5,30]. Milk is not immediately obtained during the first minutes of suckling [9,15,17]. This may result from a dominance of the sympathetic system [6,21]. However, as the sympathetic activity subsides due to activation of ductal mechanoreceptors [6,18,21], OT becomes more effective and the litter can then obtain much larger amounts of milk. In addition to adrenal CAs, the sympathetic inhibition of ME can be exerted through the innervation of the mammary gland. A reduction in the rate of milk removal is associated with increased sympathetic activity, whereas either surgical or pharmacological sympathectomy results in a faster rate of milk flow [11,21,24]. Moreover, as shown recently, neural regulation of the mammary gland involves a- and b-adre- nergic mechanisms capable of facilitating or inhibiting ME through the direct innervation of the mammary gland [24]. These central mechanisms may participate in the overall regulation of ME, but the role of suckling on its activation remains unclear. The aim of the present study was threefold: (1) to determine whether suckling inhibits ME induced by OT in urethane-anesthetized lactating rats, (2) to what extent such action may result from adrenal CAs [6] and/or through the sympathetic innervation of the mammary glands [24] and 0031-9384/01/$ – see front matter D 2001 Elsevier Science Inc. All rights reserved. PII:S0031-9384(01)00559-5 * Corresponding author. Tel.: +52-42-34-04-81; fax: +52-42-34-03-44. E-mail address: fmena@servidor.unam.mx (F. Mena). Physiology & Behavior 74 (2001) 37 – 43