Chronic Oxytocin Research Articles

Effect of chronic oxytocin-treatment on the bovine mammary gland immune system

The aim of this study was to evaluate the effect of chronic oxytocin (OT) treatment on the mammary gland immune system. In <I>Experiment I</I> fourteen healthy cows were used to study the effect of chronic intramuscular (im) OT administration on concentration of milk somatic cells and white blood cells (WBC). Cows in the OT-group (6) were im injected with 50 IU OT (5 ml) whereas animals of the C-group (6) were im injected with 5 ml of saline (9 g/l) for eight days (Day 1–8) before each milking. Milk samples were taken during normal milking time on Day 0–3, 5, 7, 9–11 and 18. Blood samples were taken immediately after each milking and analysed for WBC count, polymorphonuclear neutrophils, potassium (K), sodium (Na) and chloride (Cl) ions, and blood lactose. All milk samples were analysed for somatic cell counts (SCC), lactose, Na, Cl and electrical conductivity (EC). Furthermore mRNA expression of tumor necrosis factor-α (TNFα), interleukin (IL)-1β, IL-6, IL-8 and cyclooxygenase-2 (COX2) in milk cells were measured via real-time RT-PCR. None of the investigated milk and blood parameters changed significantly in response to the OT treatment. The mRNA-expression of TNFα decreased (<I>P</I> < 0.05) to a minimum on Day 3 in response to OT administration. IL-1β and IL-6-mRNA expression decreased (<I>P</I> < 0.05) to a minimum within three day. IL-8 and COX2 expression did not change in response to OT treatment. In <I>Experiment II</I> twelve cows, randomly divided into two groups of six, were used to investigate the effect of chronic im OT administration on mammary tissue. Cows were im administered 50 IU OT (OT-group) or 5 ml saline (9 g/l; C-group) before each milking during eight days. Biopsy samples were taken after every morning milking. The mRNA expression of various inflammatory factors and the tight junction (TJ) proteins occludin (OCLN) and zonula occludens (ZO)-1, ZO-2 and ZO-3 were measured via real-time RT-PCR. TNFα-mRNA expression decreased (Day 2 with <I>P</I> < 0.05) within the first four days of OT administration and increased (<I>P</I> < 0.05) in the C-group on Day 2. IL-1β expression levels of the OT-group increased transiently and decreased on Day 3 and in the C-group values increased significantly on Day 3 as compared to Day 0. IL-6 expression in the OT-group decreased (<I>P</I> < 0.05) to a minimum on Day 1 and increased (<I>P</I> < 0.05) as compared to Day 0 on Day 7 and increased significantly on Day 1 and Day 5 compared to Day 0 in group C. IL-8 and COX2 expression did not change in response to OT administration. The mRNA-expression of OCLN and ZO-3 decreased (<I>P</I> < 0.05) as compared to Day 0 with a minimum on Day 7. ZO-1 and ZO-2 expression did not change due to OT administration. ZO-2-mRNA expression in C-group decreased significantly on Day 2 compared to Day 0. In conclusion, chronic OT administration induced increasing SCC and EC levels in milk as well as K and lactose in blood while nearly all investigated cytokines in milk cells and mammary tissue were down regulated. The mRNA expressions of the TJ proteins OCLN and ZO-3 were down-regulated in response to the OT treatment what indicates an increasing TJ permeability. Besides the effect on TJ proteins there was no obvious change of the immunological competence of the mammary gland in response to OT. However, a more complete milk ejection should help to remove pathogens during milking.

Effects of Removing Cows from Chronic Oxytocin Use During Lactation

It is a relatively common practice on dairy farms to administer oxytocin i.m. to cows with poor milk let down at the time of milking. This practice is often perpetuated throughout a cow's lactation because of the fear that once a cow is started on oxytocin she will be so addicted that upon removal she will develop udder problems or drop considerably in milk production. Oxytocin is approved for use in milk let down but not labeled for use to increase production. If cows are started on oxytocin for poor let down but are kept on for fear of loss of production this could be construed as extra label use. The objective of this study was to test the effect of several different methods of removing cows from chronic oxytocin treatment during lactation.

Chronic oxytocin treatment mediates heart rate responses following social isolation

Chronic oxytocin treatment mediates heart rate responses following social isolation

248 PUBLICATION Pyruvate kinase activity in colon, stomach and breast tissue as a marker of malignancy

Oxytocin (OXT) has been used to prolong the luteal phase in mares, but its mechanism of action is unknown. The aim of this study was to evaluate the effect of chronic exogenous OXT administration to mid-luteal phase mares on luteal maintenance. Also, endometrial expression of prostaglandin endoperoxide synthase 2 (PTGS2), prostaglandin F2α, E2 and I2 synthases (AKR1C3, PTGES, and PTGIS), oxytocin receptor (OXTR), progesterone receptor (PGR), and estrogen receptors 1 (ESR1) and 2 (ESR2) were assessed in mares experiencing luteal maintenance 2 weeks after chronic exogenous OXT administration. Control mares (n = 5; C group) received 6 mL of saline im, whereas OXT (60 units/mare) was administered im (n = 6; OXT group), every 12 hours, on days 7 to 14 postovulation. After endometrial biopsy in groups C (Day 10) and OXT (Day 24), luteolysis occurred within 3 or 6 days, respectively. Luteal maintenance took place in 4 of 6 (67%) of OXT-treated mares. Progesterone in C group was the highest on biopsy day (P < 0.05). In OXT mares, PTGS2, ESR1 (P < 0.05), PTGES, PTGIS, PGR, and ESR2 (P < 0.01) gene transcription decreased, whereas OXTR increased (P < 0.05) in comparison with the C group. In OXT-treated mares, endometrial ESR2 protein expression decreased (P < 0.05), but OXTR increased (P < 0.05) compared with control animals. In both experimental groups, PTGS2 was mainly immunolocalized in surface epithelium, whereas AKR1C3, PTGES, PTGIS, and PGR were in surface and glandular epithelia. ESR1 and ESR2 were found in glandular epithelium and OXTR in stromal cells. High immunolabeling for PTGES, PTGIS, PGR, and OXTR and low for ESR2 was detected in endometrium of OXT-group mares with extended diestrus. Prolonged luteal function associated with chronic OXT treatment may be related to different spatial expression of OXTR and PGR in the endometrium. The observed reduction of endometrial ESR2 may be responsible for the maintenance of PGR in luminal and glandular epithelium. Also, ESR2 may attenuate the transcriptional activity of ESR1 in mare endometrium. This study offers new knowledge on the endometrial expression of ovarian steroids and OXT receptors in OXT pharmacologically induced luteal maintenance in the mare.

Effects of oxytocin administration on oxytocin release and milk ejection.

In experiment I, the effect of i.m. oxytocin (OT) injection (50 IU) on OT blood pattern was tested. Blood samples from 6 cows were collected for 2 h after OT injection either with or without milking. To test the effect of i.m. OT injection (50 IU) on milk ejection efficiency, intramammary pressure (IMP) was measured in 13 cows (experiment II). Milk ejection was induced by manual teat stimulation. After IMP increased and reached a plateau, OT was injected. In experiment III, the effect of chronic OT treatment on mammary gland sensitivity and endogenous OT release was tested. For 19 d, cows were i.m. injected at each milking with 50 IU OT (n = 13) or 5 mL of NaCl 0.9% (n = 14) 1 min before the start of udder preparation. To test mammary gland sensitivity, IMP recording was performed after a long (11 h, 7 OT cows, and 7 NaCl cows) and a short (3 h, 6 OT cows, and 7 NaCl cows) milking interval at d -1 and d 18. To test the effect of withdrawal of chronic i.m. treatment on OT release, blood sample collection was performed during evening milking at d 0 and d 19. Intramuscular oxytocin injection (experiment I) caused elevated OT blood levels observed at least for 2 h and showed an even more pronounced effect when milking was also performed. Intramuscular OT injection after teat stimulation (experiment II) caused additional milk ejection but only in 6 out of 13 cows. Withdrawal of chronic OT treatment (experiment III) did not reduce OT release during milking. However, ejection time was prolonged during OT infusion after a long milking interval. Ejection pressure tended to be lower after a short milking interval. It seems that the reduction of spontaneous milk removal after chronic OT treatment was due to reduced contractibility of myoepithelial cells in the mammary gland at a physiological range of OT concentrations.

Prolactin and oxytocin interaction in the paraventricular and supraoptic nuclei: effects on oxytocin mRNA and nitric oxide synthase.

We investigated the contribution of prolactin and oxytocin to the increase in staining for NADPH-d and oxytocin mRNA in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) observed at the end of pregnancy, or following a steroid-priming regimen that mimics the hormonal profile of late pregnant females. Ovariectomized rats received chronic implants of silastic capsules containing oestrogen and progesterone followed by progesterone removal. In experiment 1, oxytocin antagonist (OTA) was administered to rats to investigate whether intranuclear oxytocin release was necessary for NADPH-d staining. In experiments 2a and b, rats received concurrent treatment with bromocryptine (0.5 mg/day) to suppress endogenous prolactin release, and either systemic prolactin (0.5 mg once daily), or prolactin (2 micro g/ micro l), or vehicle infused twice a day into the third ventricle, or chronic oxytocin infusion (24 ng/day) for 3 days following progesterone removal. Brains were then processed for NADPH-d histochemistry. In experiment 3, the interaction of prolactin and oxytocin on oxytocin mRNA within the SON and PVN was examined. NADPH-d staining in the SON and PVN was reduced by the highest dose of the OTA, and by bromocryptine treatment. Central prolactin and oxytocin replacement completely restored NADPH-d staining in bromocryptine-treated rats. Finally, both bromocryptine and the OTA suppressed oxytocin mRNA expression and prolactin replacement restored expression levels to that of controls. Together, these data suggest that the increased capacity to produce nitric oxide in the SON and PVN during late pregnancy is dependent on prolactin stimulating oxytocin gene mRNA and hence intranuclear oxytocin release.

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 &amp; Armstrong, 1992; Gorewit et al. 1983; Lefcourt &amp; 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 &amp; 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.

Chronic Hypoosmolality Induces a Selective Decrease in Magnocellular Neurone Soma and Nuclear Size in the Rat Hypothalamic Supraoptic Nucleus

AbstractThe magnocellular neurones of the hypothalamo‐neurohypophysial system (HNS) play a vital role in the maintenance of body homeostasis by regulating oxytocin (OT) and vasopressin (VP) secretion from the posterior pituitary. During hyperosmolality, OT and VP mRNA levels are known to increase by approximately two‐fold, whereas during chronic hypoosmolality, OT and VP mRNA levels decrease to approximately 10–20% of basal levels. In these studies, we evaluated changes in cell size associated with these physiological conditions. Cell and nuclear sizes of neurones in the supraoptic nucleus (SON), the nucleus of the lateral olfactory tract (LOT) and the medial habenular nucleus (MHB) were measured from neurones identified by in situ hybridization histochemistry for βIII‐tubulin mRNA, and measurements were made from OT and AVP magnocellular neurones in the SON after phenotypic identification by immunohistochemistry. Under hypoosmolar conditions, the cell and nuclear sizes of OT and VP magnocellular neurones decreased to approximately 60% of basal values, whereas cell and nuclear sizes of OT and VP neurones in hyperosmolar rats increased to approximately 170% of basal values. In contrast, neither hyperosmolality, nor hypoosmolality significantly affected cell and nuclear sizes in the LOT and MHB. These results confirm previous studies that showed that magnocellular neurones increase cell size in response to hyperosmolar conditions and, for the first time, demonstrate a marked decrease in cell size in the SON in response to chronic hypoosmolar conditions. These dramatic changes in cell and nuclear size directly parallel changes in OT and VP gene expression in the magnocellular neurones of the SON and, consequently, are consistent with the pronounced bidirectional changes in gene expression and cellular activity found during these osmotic perturbations. Our results therefore support the concept of global alterations in the synthetic activity of magnocellular OT and AVP neurones in response to extracellular osmolality.

Chronic hypoosmolality induces a selective decrease in magnocellular neurone soma and nuclear size in the rat hypothalamic supraoptic nucleus.

The magnocellular neurones of the hypothalamo-neurohypophysial system (HNS) play a vital role in the maintenance of body homeostasis by regulating oxytocin (OT) and vasopressin (VP) secretion from the posterior pituitary. During hyperosmolality, OT and VP mRNA levels are known to increase by approximately two-fold, whereas during chronic hypoosmolality, OT and VP mRNA levels decrease to approximately 10-20% of basal levels. In these studies, we evaluated changes in cell size associated with these physiological conditions. Cell and nuclear sizes of neurones in the supraoptic nucleus (SON), the nucleus of the lateral olfactory tract (LOT) and the medial habenular nucleus (MHB) were measured from neurones identified by in situ hybridization histochemistry for beta(III)-tubulin mRNA, and measurements were made from OT and AVP magnocellular neurones in the SON after phenotypic identification by immunohistochemistry. Under hypoosmolar conditions, the cell and nuclear sizes of OT and VP magnocellular neurones decreased to approximately 60% of basal values, whereas cell and nuclear sizes of OT and VP neurones in hyperosmolar rats increased to approximately 170% of basal values. In contrast, neither hyperosmolality, nor hypoosmolality significantly affected cell and nuclear sizes in the LOT and MHB. These results confirm previous studies that showed that magnocellular neurones increase cell size in response to hyperosmolar conditions and, for the first time, demonstrate a marked decrease in cell size in the SON in response to chronic hypoosmolar conditions. These dramatic changes in cell and nuclear size directly parallel changes in OT and VP gene expression in the magnocellular neurones of the SON and, consequently, are consistent with the pronounced bidirectional changes in gene expression and cellular activity found during these osmotic perturbations. Our results therefore support the concept of global alterations in the synthetic activity of magnocellular OT and AVP neurones in response to extracellular osmolality.

Changes in NADPH-d staining in the paraventricular and supraoptic nuclei during pregnancy and lactation in rats: role of ovarian steroids and oxytocin.

Staining for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), a histochemical marker for nitric oxide synthase (NOS), is increased in the supraoptic (SON) and paraventricular (PVN) nuclei in late pregnant rats. To determine whether increases in staining were evident at other times during pregnancy and lactation the number of cells that stained for NADPH-d in the SON and PVN in rats on days 4, 12, 16, and 22 of pregnancy and on days 4, 12, and 20 of lactation was compared to that in virgin females. In a second experiment the influence of ovarian hormones on NADPH-d staining was assessed by comparing staining in the SON and PVN among ovariectomized animals exposed to either a steroid hormone replacement schedule that mimics late pregnancy (oestrogen and progesterone with progesterone removal), oestrogen alone, oestrogen and progesterone, or cholesterol alone. In the last experiment of this series staining was compared among ovariectomized animals given either oestrogen or cholesterol priming accompanied by oxytocin (OT) or vehicle infusion into the third ventricle for 7 days. The number of cells showing dense staining for NADPH-d in both the SON and PVN increased on days 12 and 22 of pregnancy and 4 and 12 of lactation compared to that observed in virgins. NADPH-d staining in these areas was also increased by both the steroid treatment that mimicked late pregnancy and chronic central OT infusion in oestrogen-primed animals. These data suggest that NADPH-d staining in the SON and PVN is increased at times when oxytocinergic cells are known to be active and that the hormonal state associated with late pregnancy is sufficient to increase NADPH-d staining.

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 pretreatment inhibits adenylyl cyclase activity in cultured rat myometrial cells.

To determine whether chronic oxytocin pretreatment inhibits adenylyl cyclase, we compared adenylyl cyclase activity in membranes prepared from cultured, immortalized rat myometrial cells that were untreated or pretreated for 24 h with oxytocin. Chronic oxytocin pretreatment (1 x 10(-5) M for 24 h) attenuated basal, guanosine triphosphate (1 x 10(-5) M)-, isoproterenol (1 x 10(-4) M)-, forskolin (1 x 10(-5) M)-, MnCl2 (20 mM)- or NaF (1 x 10(-2) M)-stimulated adenylyl cyclase activity by 27 +/- 5% to 39 +/- 11% (n = 6, p < 0.05). Oxytocin pretreatment for 2 h (n = 5) did not produce a significant effect. To understand the mechanism by which oxytocin pretreatment decreased activity of the adenylyl cyclase pathway, we compared effects of pretreatment with either oxytocin or phenylephrine on adenylyl cyclase activity and determined the effects of Gi inhibition and protein kinase C (PKC) depletion. Chronic (24 h) phenylephrine pretreatment (1 x 10(-4) M) had effects similar to those of oxytocin pretreatment (1 x 10(-5) M). PKC depletion with phorbol 12-myristate 13-acetate (1 x 10(-6) M, 41 h) prevented attenuation of adenylyl cyclase activity by oxytocin pretreatment (1 x 10(-5) M for 24 h). Inhibition of Gi by pertussis toxin pretreatment (1.25 microg/ml, 41 h) had no significant effect. These findings suggest that chronic oxytocin pretreatment desensitizes the adenylyl cyclase pathway by a cross-regulatory mechanism that involves activation of Gq and PKC.

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.

Influence of exogenously administered oxytocin on prolactin-producing cells in adult male rats as revealed by immuno-electron microscopy.

Prolactin-producing cells (PRL cells) identified by immuno-electron microscopy were studied in male rats with chronic intraperitoneal injection of synthetic oxytocin (OT). The PRL cells are usually classified into three types: the immature type containing round secretory granules about 100 nm in diameter with poorly developed cell organelles; the intermediate type containing medium-sized (150-250 nm in diameter) secretory granules with moderately developed cell organelles; and mature type containing large pleomorphic secretory granules ranging from 300 to 700 nm in diameter with well-developed cell organelles. In male rats, the intermediate type comprises typical PRL cells that constitute about 50% of all immunoreactive PRL cells. Chronic intraperitoneal OT administration to rats caused morphologically hypertrophic and hyperfunctioning PRL cells which are identified as mature type PRL cells. The frequency of occurrence of the mature type PRL cells increased after treatment. The contents of pituitary and serum PRL as measured by radioimmunoassay essentially paralleled the morphological results. These data indicate that OT may play a physiological role in PRL secretion as a releasing factor, and that OT administration causes the interconversion of the three types of PRL cells, indicating the mature type to be at the most activated state of secretory function.

Enhanced social interactions in rats following chronic, centrally infused oxytocin

Most studies investigating the behavioral effects of centrally administered oxytocin (OT) have been confined to single acute injections followed by brief behavioral observations lasting up to 90 min. The present study examines the behavioral effects of chronic, centrally administered OT in male rats observed continously for prolonged periods of time. Either artificial cerebrospinal fluid or OT was centrally infused (via osmotic minipump) to gonadally intact male rats. Behavioral observations were made on males paired with either ovariectomized or estrous females during a 6-h time period. Most striking was the observation that durations of physical contact were doubled in pairs containing OT-infused males, even in the absence of sexual interactions. Also, OT-infused males showed significantly higher levels of anogenital sniffing of females and autogrooming; however, sexual interactions were unaffected by chronic OT. Chronic OT had no effect on body temperature, analgesia, or exploratory behavior in an open field. These findings suggest that chronic OT in male rats has behavioral effects that may significantly enhance adult social (nonsexual) interactions, possibly through alterations in olfactory and somatosensory information processing.

Myometrial oxytocin receptors and prostaglandin in the parturition process in the rat.

Parturition in rats is associated with an abrupt and marked increase in myometrial oxytocin (OT) receptor concentrations. In this study, we investigated the role of myometrial OT receptors in the initiation and the process of parturition. We produced chronic OT receptor blockade during the last 3 days of gestation by administration of a specific OT antagonist at 100 micrograms/day and 300 micrograms/day. We also suppressed OT receptor formation by inhibiting prostaglandin synthesis with naproxen sodium at 2 mg/day and 5 mg/day. We found that chronic blockade of OT receptors inhibited the uterotonic response to OT in Day 22 and Day 23 pregnant rats in a dose-dependent manner. OT antagonist treatment did not prolong the gestation period. However, the duration of parturition, fetal mortality, and the mortality incidence were increased in rats treated with the high dose of the OT antagonist compared to controls. Naproxen sodium at both dosage levels prolonged gestation by 24 h or longer, doubled the duration of parturition, and markedly increased fetal mortality and mortality incidence. Combined OT antagonist and naproxen treatment produced adverse outcomes similar to that produced by naproxen treatment alone. Myometrial OT receptor concentrations were markedly increased in all rats immediately postpartum, ranging from 210 to 425 fmol/mg protein compared to the 50 to 100 fmol/mg found in Day 21 and Day 22 pregnant rats. Correlation analyses between OT receptor concentrations and various parameters associated with gestation and parturition showed that there was a correlation between low OT receptor concentrations and long gestation period, prolonged parturition, and high fetal mortality rate.(ABSTRACT TRUNCATED AT 250 WORDS)

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.