Chronic Oxytocin Treatment Research Articles

Chronic oxytocin treatment causes reduced milk ejection in dairy cows.

The major milk fraction stored in the bovine udder, the alveolar milk, is not available for milk removal before being actively shifted to the cisternal cavities by the milk ejection reflex (Knight et al. 1994; Pfeilsticker et al. 1996). Tactile teat stimulation, provided by the liner throughout milking, causes continuous release of oxytocin from the neuro-pituitary into the blood circulation, which induces myoepithelial contraction and shifting of alveolar milk into the cistern until the end of milking (Bruckmaier et al. 1994; Crowley & Armstrong, 1992; Gorewit et al. 1983; Lefcourt & Akers, 1983). However, milk ejection during machine milking is not complete. A residual milk fraction of 10–30% remains in the udder and is only removed after administration of supraphysiological amounts of oxytocin, usually at least 10 i.u. of oxytocin injected i.v. (Bruckmaier & Blum, 1998). In dairy practice, exogenous oxytocin is often used at high dosages to treat disturbed or incomplete milk ejection. It is reported by farmers and veterinarians that after long-term use of exogenous oxytocin animals become addicted to the treatment and withdrawal of oxytocin causes reduced milk ejection.

Short-term increase and long-term decrease of blood pressure in response to oxytocin-potentiating effect of female steroid hormones.

To investigate how the effects of oxytocin on blood pressure are influenced by female sex hormones, oxytocin (1 mg/kg, s.c.) was given to intact cycling and ovariectomized (OVX) female rats. Oxytocin caused a transient increase in blood pressure, most pronounced during proestrus (p < 0.01) and estrus (p < 0.01). This increase was partially antagonized by an oxytocin antagonist. When oxytocin was given for 5 days, blood pressure decreased (intact rats: 123+/-1.5 vs. 130+/-1.3 mm Hg; p < 0.001, OVX rats: 120+/-3.0 vs. 129+/-1.1 mm Hg; p < 0.001). This decrease, not abolished by the oxytocin antagonist, persisted for 3 weeks in intact rats and for 8 days in OVX rats. If oxytocin treatment of OVX rats continued, a nadir of 12 mm Hg (118+/-1.7 mm Hg; p < 0.001) was reached after 8 days. Thereafter heart rate decreased significantly (p < 0.05). One daily oxytocin injection for 12 days to OVX rats decreased blood pressure for 3 weeks, as in intact rats. These results show that acute and chronic oxytocin treatment cause opposite effects on blood pressure, and that these effects are modified by female sex hormones.

Chronic oxytocin treatment during late gestation and lactation impairs development of rat offspring

The nonapeptide oxytocin (OT) plays an important role in timing and course of parturition, and in milk ejection during lactation. Exogenously enhanced OT levels were reported to impair body development of rat offspring at birth and during postnatal stages. In the present study, this effect was further investigated by giving pregnant rats of postcoital day 17 a SC implant that delivers small amounts of OT for 2 months (approximately threefold enhancement of OT levels), and by introducing a crossfostering protocol for the offspring. A slightly reduced body weight of 5 to 7% was again observed in pups born to OT-implanted dams. When reared postnatally by OT-treated mothers, pups lost weight gain (− 7 to −10%). During the weaning period, however, body size caught up with that of control animals. When nursed by an untreated mother, this recovery took place before that period. Growth of control offspring was also hampered when placed with OT-treated mothers, but these pups failed to recover from low body weights which lasted up to at least 70 days of age (−7%). Daily urine production of the pups born of and reared by the OT-treated mothers was reduced at 1 month of age, but this effect was only transient and had disappeared at 70 days of age. Notwithstanding, the recovery of body growth, brain sizes, and cerebellar DNA, i.e., cell content was reduced in the pups born and reared by OT-treated mothers, indicative of a lasting effect on brain development. Such late brain changes were not observed in pups of OT-treated mothers nursed by untreated mothers, and in control pups nursed by both types of mothers. In conclusion, one might say that physiologically enhanced levels of maternal OT can induce subtle alterations in brain development that are potentially indicative for lasting physiological and behavioral changes in the offspring.

Peripheral oxytocin treatment modulates central dopamine transmission in the mouse limbic structures

The effects of subcutaneous (s.c.) oxytocin treatment have been investigated on various parameters of dopaminergic neurotransmission in basal forebrain structures (nucleus olfactorius posterior + nucleus accumbens + septum) of the mouse. Acute oxytocin treatment failed to influence dopamine utilization in the basal forebrain. Following chronic injections of oxytocin (0.2 mg/kg) for 8 8 days, the neuropeptide decreased dopamine utilization. Neither in vivo nor in vitro oxytocin treatment was capable of influencing the in vitro uptake of [(3)H]dopamine in basal forebrain slices. The spontaneous release of [(3)H]dopamine (in the presence of 4.2 mM K(+)) from basal forebrain tissue slices was not affected by in vitro or acute or chronic in vivo oxytocin treatment. The stimulated release of [(3)H]dopamine (in the presence of 30 mM K(+)) was significantly inhibited by chronic in vivo oxytocin administration. Chronic oxytocin treatment decreased the B(max) value of [(3)H]spiroperidol binding in the basal forebrain. The dissociation constant (K(d)) of [(3)H]spiroperidol binding was not influenced by oxytocin. The data indicate that peripheral oxytocin treatment is capable of modifying dopaminergic neurotransmission in mouse basal forebrain regions.