Acta Physiol Scand 1990, 140, 295-296
Feeding-induced oxytocin release in dairy cows K. S V E N N E R S T E N , L. NELSON" and K. UVNAS-MOBERG? Department of Animal Nutrition and Management, Swedish University of Agricultural Sciences, Uppsala, "Alfa-Lava1 Agri International AB Research, Tumba, and tDepartment of Pharmacology, Karolinska Institute, Stockholm, Sweden In addition to being released upon suckling (Gorewit et al. 1983), oxytocin is released in response to feeding in dogs and sows (Uvnas-Moberg et al. 1985). A feeding-related release of oxytocin has not been demonstrated in dairy cows, although such an effect could explain why feeding in connection with machine milking facilitates milk let-down (Brandsma 1978). To investigate this hypothesis two different experimental series were performed on two separate groups of four non-pregnant cows. All cows had passed their peak lactation and were fed individually 1.5 h after milking. All treatments were performed in the same order and at the same time for all cows. A semipermanent polyvinyl chloride catheter was inserted into the jugular vein and attached to the back of the animal. When not in use, the catheter was filled with 0.9% NaCl solution containing 50 I U ml-' heparin. In the first series, blood samples were drawn 20 and 10min before and at 5, 20 and 60min after the morning feeding. In this experiment samples also were taken as soon as the tender arrived at the barn, followed by a second sample 10 rnin later. In series 2 a more frequent blood sampling was performed, with samples taken 30, 15 and 5 rnin before and 0,5, 10, 15, 20, 25, 30, 40, 50 and 60 rnin after morning feeding. Ten millilitres of blood was collected on each occasion and placed in ice-cold tubes containing heparin (50 I U m1-I) and trasylol (400 IU ml-l). Plasma concentrations of oxytocin were measured by radioimmunoassay after purification using Sep-Pak C,, cartridges (Stock & Uvnas-Moberg 1988). When studying individual experiments oxytocin levels were elevated 5 min after feeding in 10 of the 16 experiments performed in series 1, but no significant difference was found using Student's paired t-test. In series 2, however, significantly (P< 0.01) 'higher oxytocin levels were found following feeding, comparing sample - 15 with 5 rnin (Fig. 1). Thus we have for the first time been able to demonstrate a feeding-
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Received 31 May 1990, accepted 13 July 1990. Correspondence : Kerstin Svennersten, Department of Animal Nutrition and Management, Swedish University of Agricultural Sciences, Box 7024, S-750 07 Uppsala, Sweden.
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Sampling time, rnin
Fig. 1. Plasma levels of oxytocin (PM) in series 2 (mean SD). Samples were taken before feeding (- 30 to - 0 rnin), when cows were eating ( 5 to 25 min) and after feeding (+30 to +60 min). **P < 0.01 (Student's t-test comparing levels at - 15 and 5 min).
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associated oxytocin release in dairy cows. However, it should be mentioned that attempts were made to record a feeding-related output of oxytocin during the 1960s. With the less sensitive biological method used at that time no effect was found (Folley & Knaggs 1966). The mechanism behind the feeding-related release of oxytocin is unknown. It is possible that nervous pathways connecting the mouth and the paraventricular (PVN) and supraoptic (SON) nuclei are activated during feeding. Alternatively, a vagovagal reflex may contribute to the effect. Thus electrical afferent vagal nerve stimulation and systemic administration of cholecystokinin (CCK) octapeptide increase the circulating levels of oxytocin (an efect which is
295
296
K. Svennersten, L. Nelson and K. Uvnas-Moberg
blocked by vagotomy), demonstrating the presence of an afferent neural link between the stomach and neurohypophysis (Verbalis et al. 1986, Stock & UvnasMoberg 1988). Indeed, a specific projection with inhibin-/I as transmitter has been demonstrated from the nucleus tractus solitarius to the PVN (Sawchenko et ai. 1988). Since CCK is released during feeding, information from the gut on food intake could influence the activity of the oxytocinergic neurons by this pathway. It has been observed in experiments in which cows were fed concentrate during milking that milk ejection is facilitated and that the amount of residual milk is diminished (Brandsma 1978). The present finding of a feeding-associated oxytocin release ma!- constitute a physiological explanation for this effect. In the first experimental series oxytocin levels were elevated in the first sample collected in eight of the 16 experiments. Since the tender arrived at the barn a t this time point, the increase might reflect a conditioned feeding-related release of oxytocin, since cows habitually received food as soon as the tender arrived. In other species, such as lactating ewes, a conditioned type of oxytocin release has been demonstrated (Fuchs e l al. 1987). This work was supported by grants from Alfa-Lava1 Agri International AB, Tumba, Sweden, and the Swedish Council for Forestry and .4gricultural Research, Stockholm, Sweden.
REFERENCES BRANDSMA, S. 1978. The relation between milking, residual milk and milk yield. I n : Proceedings of the International Symposium on Machine Milking, 17th
.4nnual .Veering, pp. 47-56. National Mastitis Council, Louisville, Kentucky, USA. FOLLEY,S.J. & KNAGGS,G.S. 1966. Milk-ejection activitj- (oxytocin) in the external jugular vein blood of the cow, goat and sow, in relation to the stimulus of milking or suckling. f Endocrinol 34, 197-214. FUCHS, A,-R., AYROMLOOI, J. & RASMUSSEN, A.B. 1987. Oxytocin response to conditioned and nonconditioned stimuli in lactating ewes. Biol Reprod 37, 301-305. GOREWJT, R.C., WACHS,E.A., SAGI,R. & MERRILL, W.G. 1983. Current concepts in the role of oxytocin in milk ejection. 3 Dairy Sci 66, 22362250. SAWCHENKO, P.E., PLOTSKY, P.M., PFEIFFER,S.W., CUNNINGHAM JR, E.T., VAUGHAN, J., RIVIER,J. & V ~ L E ,u'. 1988. Inhibin-/I in central neural pathways involved in the control of oxytocin secretion. Nature 334, 615-617. K . 1988. Increased STOCK, S. & UVNAS-MOBERG, plasma levels of oxytocin in response to afferent electrical stimulation of the sciatic and vagal nerves and in response to touch and pinch in anaesthetized rats. Acta Physiol Scand 132, 29-34. K., STOCK,S., ERIKSSON,M., LINC'VNKS-MOBERG, DEN,.4., EINARSSON, S. & KUNAVONGKRIT, A. 1985. Plasma levels of oxytocin increase in response to suckling and feeding in dogs and cows. Acta Physiol Scand 124, 391-398. VERBALIS, J.G., MCCANN,M.J., MCHALE,C.M. & STRJCKER, E.M. 1986. Oxytocin secretion in response to cholecystokinin and food : differentiation of nausea from satiety. Science 232, 1417-1419.
Feeding-induced oxytocin release in dairy cows K. S V E N N E R S T E N , L. NELSON" and K. UVNAS-MOBERG? Department of Animal Nutrition and Management, Swedish University of Agricultural Sciences, Uppsala, "Alfa-Lava1 Agri International AB Research, Tumba, and tDepartment of Pharmacology, Karolinska Institute, Stockholm, Sweden In addition to being released upon suckling (Gorewit et al. 1983), oxytocin is released in response to feeding in dogs and sows (Uvnas-Moberg et al. 1985). A feeding-related release of oxytocin has not been demonstrated in dairy cows, although such an effect could explain why feeding in connection with machine milking facilitates milk let-down (Brandsma 1978). To investigate this hypothesis two different experimental series were performed on two separate groups of four non-pregnant cows. All cows had passed their peak lactation and were fed individually 1.5 h after milking. All treatments were performed in the same order and at the same time for all cows. A semipermanent polyvinyl chloride catheter was inserted into the jugular vein and attached to the back of the animal. When not in use, the catheter was filled with 0.9% NaCl solution containing 50 I U ml-' heparin. In the first series, blood samples were drawn 20 and 10min before and at 5, 20 and 60min after the morning feeding. In this experiment samples also were taken as soon as the tender arrived at the barn, followed by a second sample 10 rnin later. In series 2 a more frequent blood sampling was performed, with samples taken 30, 15 and 5 rnin before and 0,5, 10, 15, 20, 25, 30, 40, 50 and 60 rnin after morning feeding. Ten millilitres of blood was collected on each occasion and placed in ice-cold tubes containing heparin (50 I U m1-I) and trasylol (400 IU ml-l). Plasma concentrations of oxytocin were measured by radioimmunoassay after purification using Sep-Pak C,, cartridges (Stock & Uvnas-Moberg 1988). When studying individual experiments oxytocin levels were elevated 5 min after feeding in 10 of the 16 experiments performed in series 1, but no significant difference was found using Student's paired t-test. In series 2, however, significantly (P< 0.01) 'higher oxytocin levels were found following feeding, comparing sample - 15 with 5 rnin (Fig. 1). Thus we have for the first time been able to demonstrate a feeding-
+
Received 31 May 1990, accepted 13 July 1990. Correspondence : Kerstin Svennersten, Department of Animal Nutrition and Management, Swedish University of Agricultural Sciences, Box 7024, S-750 07 Uppsala, Sweden.
11 T
10 -
Ic, .-
0
$
9-
a-
I
h
7-
6-
5/
L
d
I
I
-20
I
I
0
I
I
I
20
I
I
40
!
I
60
Sampling time, rnin
Fig. 1. Plasma levels of oxytocin (PM) in series 2 (mean SD). Samples were taken before feeding (- 30 to - 0 rnin), when cows were eating ( 5 to 25 min) and after feeding (+30 to +60 min). **P < 0.01 (Student's t-test comparing levels at - 15 and 5 min).
+
+
+
associated oxytocin release in dairy cows. However, it should be mentioned that attempts were made to record a feeding-related output of oxytocin during the 1960s. With the less sensitive biological method used at that time no effect was found (Folley & Knaggs 1966). The mechanism behind the feeding-related release of oxytocin is unknown. It is possible that nervous pathways connecting the mouth and the paraventricular (PVN) and supraoptic (SON) nuclei are activated during feeding. Alternatively, a vagovagal reflex may contribute to the effect. Thus electrical afferent vagal nerve stimulation and systemic administration of cholecystokinin (CCK) octapeptide increase the circulating levels of oxytocin (an efect which is
295
296
K. Svennersten, L. Nelson and K. Uvnas-Moberg
blocked by vagotomy), demonstrating the presence of an afferent neural link between the stomach and neurohypophysis (Verbalis et al. 1986, Stock & UvnasMoberg 1988). Indeed, a specific projection with inhibin-/I as transmitter has been demonstrated from the nucleus tractus solitarius to the PVN (Sawchenko et ai. 1988). Since CCK is released during feeding, information from the gut on food intake could influence the activity of the oxytocinergic neurons by this pathway. It has been observed in experiments in which cows were fed concentrate during milking that milk ejection is facilitated and that the amount of residual milk is diminished (Brandsma 1978). The present finding of a feeding-associated oxytocin release ma!- constitute a physiological explanation for this effect. In the first experimental series oxytocin levels were elevated in the first sample collected in eight of the 16 experiments. Since the tender arrived at the barn a t this time point, the increase might reflect a conditioned feeding-related release of oxytocin, since cows habitually received food as soon as the tender arrived. In other species, such as lactating ewes, a conditioned type of oxytocin release has been demonstrated (Fuchs e l al. 1987). This work was supported by grants from Alfa-Lava1 Agri International AB, Tumba, Sweden, and the Swedish Council for Forestry and .4gricultural Research, Stockholm, Sweden.
REFERENCES BRANDSMA, S. 1978. The relation between milking, residual milk and milk yield. I n : Proceedings of the International Symposium on Machine Milking, 17th
.4nnual .Veering, pp. 47-56. National Mastitis Council, Louisville, Kentucky, USA. FOLLEY,S.J. & KNAGGS,G.S. 1966. Milk-ejection activitj- (oxytocin) in the external jugular vein blood of the cow, goat and sow, in relation to the stimulus of milking or suckling. f Endocrinol 34, 197-214. FUCHS, A,-R., AYROMLOOI, J. & RASMUSSEN, A.B. 1987. Oxytocin response to conditioned and nonconditioned stimuli in lactating ewes. Biol Reprod 37, 301-305. GOREWJT, R.C., WACHS,E.A., SAGI,R. & MERRILL, W.G. 1983. Current concepts in the role of oxytocin in milk ejection. 3 Dairy Sci 66, 22362250. SAWCHENKO, P.E., PLOTSKY, P.M., PFEIFFER,S.W., CUNNINGHAM JR, E.T., VAUGHAN, J., RIVIER,J. & V ~ L E ,u'. 1988. Inhibin-/I in central neural pathways involved in the control of oxytocin secretion. Nature 334, 615-617. K . 1988. Increased STOCK, S. & UVNAS-MOBERG, plasma levels of oxytocin in response to afferent electrical stimulation of the sciatic and vagal nerves and in response to touch and pinch in anaesthetized rats. Acta Physiol Scand 132, 29-34. K., STOCK,S., ERIKSSON,M., LINC'VNKS-MOBERG, DEN,.4., EINARSSON, S. & KUNAVONGKRIT, A. 1985. Plasma levels of oxytocin increase in response to suckling and feeding in dogs and cows. Acta Physiol Scand 124, 391-398. VERBALIS, J.G., MCCANN,M.J., MCHALE,C.M. & STRJCKER, E.M. 1986. Oxytocin secretion in response to cholecystokinin and food : differentiation of nausea from satiety. Science 232, 1417-1419.
