Intravenous administration of oxytocin in rats acutely decreases deprivation-induced chow intake,but it fails to affect consumption of palatable solutions

Despite its limited ability to cross the blood-brain barrier, peripherally administered oxytocin (OT) acutely decreases food intake, most likely via the brainstem and hypothalamic mechanisms. Studies performed to date have focused mainly on the effects of subcutaneous or intraperitoneal OT on the consumption of only solid calorie-dense diets (either standard or high-fat), whereas it is unknown whether, similarly to central OT, peripherally administered peptide reduces intake of calorie-dilute and non-caloric palatable solutions. In this project, we established that 0.1 μg/kg intravenous (IV) OT is the lowest anorexigenic dose, decreasing deprivation-induced standard chow intake by ca. 40% in rats and its effect does not stem from aversion. We then used this dose in paradigms in which effects of centrally acting OT ligands on consumption of palatable solutions had been previously reported. We found that IV OT did not change episodic intake of individually presented palatable solutions containing 10% sucrose, 0.1% saccharin, combined 10% sucrose-0.1% saccharin or 4.1%. Intralipid and it failed to affect daily scheduled consumption of a sucrose solution in non-deprived rats. In a two-bottle choice test, IV OT did not shift animals’ preference from sucrose to Intralipid. Finally, OT injected IV prior to the simultaneous presentation chow and a sucrose solution in food-deprived rats significantly decreased chow intake, whereas sugar water consumption remained unchanged. We conclude that IV OT reduces deprivation-induced chow intake without causing aversion, but the dose effective in decreasing energy-driven consumption of high-calorie food fails to affect consumption of palatable calorie-dilute solutions.     

Effect on fertility of human chorionic gonadotrophin and uterine lavage with oxytocin performed after mating in Arabian barren mares

The objective of the present study was to evaluate the beneficial effect of hCG injected immediately after mating in Arabian barren mares treated with uterine lavage and oxytocin. Arabian barren mares (n = 36) with PMIE were subjected to detailed clinical examinations including palpation per rectum, vaginoscopy, and cytological examination. After mating the 36 mares were randomly divided into four groups. The mares in group 1 (n = 10) were immediately after breeding injected with hCG 3000 IU IM. Uterine lavage with 1 L of N-saline containing 4 million IU of crystalline penicillin and 4 g of streptomycin sulphate was performed 4 h after breeding. Then mares received two injections of oxytocin 40 IU IM 2 h apart after 6 h of mating. Mares in group 2 (n = 10) treated with uterine lavage and oxytocin as group 1. While mares in group 3 (n = 10) received uterine lavage only. A control group (n = 6) as group 4 did not received any treatment. The results of clinical examination indicated that 69.4% of PMIE mares were harboring severe endometritis and 30.6% with a moderate form of endometritis. Significant (P < 0.01) increase in lymphocytes were founded in barren mares included in this study. Higher pregnancy rate (P < 0.01) was founded in Arabian barren mares 80% injected with hCG immediately after breeding and uterine lavage and oxytocin. No significant difference was found in mares received uterine lavage and oxytocin and uterine lavage only. In a conclusion, administration of hCG immediately after mating and intrauterine lavage containing antibiotics performed 4 h and two injections of oxytocin 40 IU IM 2 h apart after 6 h of mating had improved fertility of Arabian barren mares.     

Design and optimization of potent, selective antagonists of Oxytocin

A novel series of Oxytocin antagonists are described. This series was identified through pharmacophoric overlap of in-house and literature antagonists. Subsequent optimization led to a series of potent, selective antagonists. Several analogues displayed oral bioavailability in vivo in the rat.     

Hormonal regulation of agonistic and affiliative behavior in female mongolian gerbils (Meriones unguiculatus)

Ovarian steroids and oxytocin (OT) have been implicated in the regulation of social behaviors. The purpose of the present study was to examine hormonal substrates of aggression and affiliation in the female Mongolian gerbil (Meriones unguiculatus), a highly social, monogamous rodent. Sexually naive adult females were paired with sexually experienced males for 48 h and their interactions videotaped. Females were gonadally intact and tested during vaginal estrus (INT) or ovariectomized and observed after the following treatments, administered by means of sc injections: EBEB (7 days of estradiol-benzoate); EBP (2 days of EB followed by progesterone), SALEB (saline, days 1-5 then 2 days of EB), OTEB (OT for days 1-5 then 2 days of EB); OTOIL (OT for days 1-5 then 2 days of OIL); or SALOIL (saline days 1-5 then 2 days of OIL). During the first hour of pairing INT females displayed higher levels of affiliation and lower levels of sniffing and agonistic behavior than SALOIL females. All hormonal treatments reduced agonistic behaviors when compared to SALOIL, although none of the hormonal treatments restored affiliation to INT levels. During the 48-h test overt aggression varied by treatment with INT, EBEB, EBP, and OTEB females displaying lower levels than SALOIL, while all groups displayed similar levels of affiliation. The results indicate that OT and E play a significant role in regulating male-directed aggressive behavior in females and that the presence of ovarian hormones as well as OT can increase affiliation during initial contact. Over a sustained period of cohabitation social cues appear to be more important in regulating affiliation than gonadal hormones.     

Single exon structures of the oxytocin/vasopressin superfamily peptides of octopus

Two genes of the oxytocin/vasopressin superfamily in the cephalopod Octopus vulgaris, cephalotocin (CT) and octopressin (OP), lack introns and consist of a single exon in their protein-coding regions, which is unlike the 2 intron-3 exon structures in most vertebrates and Lys-conopressin in a pond snail Lymnaea stagnalis. Octopus may have lost introns during the evolutionary process in mollusks. mRNA that had deleted 202 bp from preproCT cDNA (CT-del) was also expressed in the brain. The deletion occurred in the central part of neurophysin. Immunohistochemical studies suggest that a translational product of CT-del mRNA may not be present in a stable form due to the loss of neurophysin. Genomic Southern blot analysis revealed that a single copy of each of OP-, CT-, and CT-del-genes was present in the genome.     

Rem sleep,early experience,and the development of reproductive strategies

We hypothesize that rapid eye movement or REM sleep evolved, in part, to mediate sexual/reproductive behaviors and strategies. Because development of sexual and mating strategies depends crucially on early attachment experiences, we further hypothesize that REM functions to mediate attachment processes early in life. Evidence for these hypotheses comes from (1) the correlation of REM variables with both attachment and sexual/reproductive variables; (2) attachment-related and sex-related hormonal release during REM; (3) selective activation during REM of brain sites implicated in attachment and sexual processes; (4) effects of maternal deprivation on REM; (5) effects of REM deprivation on sexual behaviors; and (6) the REM-associated sexual excitation. To explain why we find associations among REM sleep, attachment, and adult reproductive strategies, we rely on recent extensions of parent-offspring conflict theory. Using data from recent findings on genomic imprinting, Haig (2000) and others suggest that paternally expressed genes are selected to promote growth of the developing fetus/child at the expense of the mother, while maternally expressed genes counter these effects. Because developmental REM facilitates attachment-related outcomes in the child, developmental REM may be regulated by paternally expressed genes. In that case, REM may have evolved to support the “aims” of paternal genes at the expense of maternal genes. Patrick McNamara, Ph.D., is an assistant professor of neurology at Boston University School of Medicine and a member of the Department of Neurology at the Boston VA Medical Center. He specializes in study of catecholaminergic mechanisms of cognitive disorders in Parkinson’s and related disorders. He has a long-standing interest in anthropological and evolutionary approaches to medicine and to human cognition. His recent book Mind and Variability applied Darwinian models to problems of memory and identity. He is currently writing a book on the evolutionary psychology of sleep and dreams. Sanford Auerbach, M.D., is an associate professor of neurology and psychiatry at Boston University School of Medicine and medical director of the Neurophysiology Laboratories at the Boston Medical Center. He is a behavioral neurologist and a board-certified sleep specialist. He is also director of the Sleep Disorders Center at Boston Medical Center. He has been associated with the NIH-sponsored Sleep Heart Health Study and other sleep-related research. He has been a member of the executive committee of the Sleep Section of the American Academy of Neurology and a past chair of the Neurology section of the American Sleep Disorders Association. Jayme Dowdall is a medical student at Boston University School of Medicine who plans to specialize in molecular approaches to medical and sleep disorders.     

Sensory and physiological determinants of maternal behavior in the goat (Capra hircus)

Maternal behavior in the goat appears at the time of parturition, partly under the activating influence of vaginocervical stimulation. Mothers actively lick their neonate and rapidly establish a selective bond with their kid through olfactory recognition. They also develop visual and acoustic recognition of the kid within 4 h following birth. Acoustic recognition is present at 48 h. The establishment of maternal recognition can be impaired by underfeeding during the second half of pregnancy. There is no indication that the mechanisms controlling the onset of maternal behavior and bonding are different from those reported in sheep, despite the fact that lambs start to follow their mother within a few hours after birth and kids hide for about a week. During lactation, the cues provided by the kid are necessary for the maintenance of maternal responsiveness, but suckling itself does not appear of primary importance. The presence of the kid also modulates the hormonal response to udder stimulation and influences recovery of postpartum sexual activity when kidding (i.e. birthing) takes place in autumn. Finally, the rapid establishment of mutual attachment between mother goats (does) and their kids offers the possibility to investigate an aspect of mother-young affiliation that is not present in many laboratory species.     

Somato-dendritic mechanisms underlying the electrophysiological properties of hypothalamic magnocellular neuroendocrine cells: A multicompartmental model study

Magnocellular neuroendocrine cells (MNCs) of the hypothalamus synthesize the neurohormones vasopressin and oxytocin, which are released into the blood and exert a wide spectrum of actions, including the regulation of cardiovascular and reproductive functions. Vasopressin- and oxytocin-secreting neurons have similar morphological structure and electrophysiological characteristics. A realistic multicompartmental model of a MNC with a bipolar branching structure was developed and calibrated based on morphological and in vitro electrophysiological data in order to explore the roles of ion currents and intracellular calcium dynamics in the intrinsic electrical MNC properties. The model was used to determine the likely distributions of ion conductances in morphologically distinct parts of the MNCs: soma, primary dendrites and secondary dendrites. While reproducing the general electrophysiological features of MNCs, the model demonstrates that the differential spatial distributions of ion channels influence the functional expression of MNC properties, and reveals the potential importance of dendritic conductances in these properties. Action Editor: Eric De Schutter     

Physiology of spontaneous [Ca2+]i oscillations in the isolated vasopressin and oxytocin neurones of the rat supraoptic nucleus

The magnocellular vasopressin (AVP) and oxytocin (OT) neurones exhibit specific electrophysiological behaviour, synthesise AVP and OT peptides and secrete them into the neurohypophysial system in response to various physiological stimulations. The activity of these neurones is regulated by the very same peptides released either somato-dendritically or when applied to supraoptic nucleus (SON) preparations in vitro. The AVP and OT, secreted somato-dendritically (i.e. in the SON proper) act through specific autoreceptors, induce distinct Ca²⁺ signals and regulate cellular events. Here, we demonstrate that about 70% of freshly isolated individual SON neurones from the adult non-transgenic or transgenic rats bearing AVP (AVP-eGFP) or OT (OT-mRFP1) markers, produce distinct spontaneous [Ca²⁺]_i oscillations. In the neurones identified (through specific fluorescence), about 80% of AVP neurones and about 60% of OT neurones exhibited these oscillations. Exposure to AVP triggered [Ca²⁺]_i oscillations in silent AVP neurones, or modified the oscillatory pattern in spontaneously active cells. Hyper- and hypo-osmotic stimuli (325 or 275 mOsmol/l) respectively intensified or inhibited spontaneous [Ca²⁺]_i dynamics. In rats dehydrated for 3 or 5 days almost 90% of neurones displayed spontaneous [Ca²⁺]_i oscillations. More than 80% of OT-mRFP1 neurones from 3 to 6-day-lactating rats were oscillatory vs. about 44% (OT-mRFP1 neurones) in virgins. Together, these results unveil for the first time that both AVP and OT neurones maintain, via Ca²⁺ signals, their remarkable intrinsic in vivo physiological properties in an isolated condition.     

Maternal care effects on the development of a sexually dimorphic motor system: The role of spinal oxytocin

Maternal licking in rats affects the development of the spinal nucleus of the bulbocavernosus (SNB), a sexually dimorphic motor nucleus that controls penile reflexes involved with copulation. Reduced maternal licking results in decreased motoneuron number, size, and dendritic length in the adult SNB, as well as deficits in adult male copulatory behavior. Our previous findings that licking-like tactile stimulation influences SNB dendritic development and upregulates Fos expression in the lumbosacral spinal cord suggest that afferent signaling is changed by differences in maternal stimulation. Oxytocin afferents from the hypothalamus are a possible candidate, given previous research that has shown oxytocin is released following sensory stimulation, oxytocin modulates excitability in the spinal cord, and is a pro-erectile modulator of male sex behavior. In this experiment, we used immunofluorescence and immediate early gene analysis to assess whether licking-like tactile stimulation of the perineum activated parvocellular oxytocinergic neurons in the hypothalamus in neonates. We also used enzyme immunoassay to determine whether this same stroking stimulation produced an increase in spinal oxytocin levels. We found that stroking increased Fos immunolabeling in small oxytocin-positive cells in the paraventricular nucleus of the hypothalamus, in comparison to unstroked or handled control pups. In addition, 60 s of licking-like perineal stimulation produced a transient 89% increase in oxytocin levels in the lumbosacral spinal cord. Together, these results suggest that oxytocin afferent activity may contribute to the effects of early maternal care on the masculinization of the SNB and resultant male copulatory behavior.