Functional magnetic resonance imaging shows oxytocin activates brain regions associated with mother-pup bonding during suckling

Oxytocin is released in the maternal brain during breastfeeding and may help strengthen the mother-infant relationship. Here, we used functional magnetic resonance imaging to determine whether oxytocin modulates brain activity in postpartum day 4-8 dams receiving suckling stimulation. During imaging sessions, dams were exposed to pup suckling before and after administration of an oxytocin receptor antagonist. Another group of dams received oxytocin alone. Changes in brain activation in response to suckling closely matched that elicited by oxytocin administration. The overlapping brain areas included the olfactory system, nucleus accumbens, insular cortex, prefrontal cortex, ventral tegmental area, cortical amygdala, and several cortical and hypothalamic nuclei. Blockade of oxytocin receptors largely attenuated activation in these regions. The data suggest that oxytocin may strengthen mother-infant bond formation partly by acting through brain areas involved in regulating olfactory discrimination, emotions, and reward

Behavioral and neuroendocrine consequences of social subjugation across adolescence and adulthood

BACKGROUND: Social subjugation is a very significant and natural stressor in the animal kingdom. Adult animals defeated and subjugated during establishment of dominance hierarchies or territorial encounters can be highly submissive in future agonistic interactions. While much is know about the biological and behavioral consequences of winning and losing fights in adulthood, little is known about adolescence; a developmental period noted for impulsivity and heightened agonistic behavior. The present studies were undertaken to determine if the behavioral and neuroendocrine consequences of social subjugation are comparable in adolescent versus adult Syrian golden hamsters (Mesocricetus auratus). Male siblings were studied from adolescence into adulthood following exposure to counterbalanced episodes of either a benign stressor, i.e., isolation in a novel cage, or the more severe stressor of social subjugation. RESULTS: As adults, hamsters with a history of social subjugation in adolescence show high levels of aggression toward intruders as compared to siblings subjugated in adulthood. Sibling controls subjugated in adulthood are highly submissive with little or no aggressive behavior. However, when subjugated in adulthood, hamsters with the earlier history of subjugation are no different than their sibling controls, i.e., adult subjugation promotes submissive behavior. Sexual motivation is high in adult hamsters with adolescent subjugation and testosterone levels remained stable over adulthood. In contrast, sibling controls subjugated in adulthood show lower levels of sexual motivation and reduced levels of testosterone. Release of cortisol during agonistic encounters is blunted in animals subjugated in adolescence but not adulthood. Measures of anxiety are reduced in hamsters with adolescent subjugation as compared to their sibling controls. CONCLUSION: These data demonstrate a pronounced difference in behavior and neuroendocrinology between adolescent and adult hamsters in their response to social subjugation and suggest adolescence is a resilient period in development

Behavioral and neurobiological consequences of social subjugation during puberty in golden hamsters

In golden hamsters, offensive aggression is facilitated by vasopressin and inhibited by serotonin. We tested whether these neurotransmitter systems respond to modifications resulting from the stress of threat and attack (i.e., social subjugation) during puberty. Male golden hamsters were weaned at postnatal day 25 (P25), exposed daily to aggressive adults from P28 to P42, and tested for offensive aggression as young adults (P45). The results showed a context-dependent alteration in aggressive behavior. Subjugated animals were more likely to attack younger and weaker intruders than nonsubjugated controls. Conversely, subjugated animals were less likely to attack animals of similar size and age. After testing, the animals were killed, and their brains were collected to determine whether these behavioral changes are underlined by changes in the vasopressin and serotonin systems. Social subjugation resulted in a 50% decrease in vasopressin levels within the anterior hypothalamus, a site involved in the regulation of aggression. Furthermore, whereas the density of vasopressin-immunoreactive fibers within the area was not significantly altered in subjugated animals, the number of serotonin-immunoreactive varicosities within the anterior hypothalamus and lateral septum was 20% higher in subjugated animals than in their controls. These results establish puberty as a developmental period sensitive to environmental stressors. Furthermore, the results show that changes in the vasopressin and serotonin systems can correlate with behavioral alterations, supporting the role of these two neurotransmitters in the regulation of aggression

Estrogen influences cocaine-induced blood oxygen level-dependent signal changes in female rats

We investigated the effect of estrogen on cocaine-induced brain activity using blood oxygen level-dependent (BOLD) magnetic resonance imaging. Ovariectomized (Ovx) rats without estrogen and Ovx rats with estrogen (Ovx+E) were given a single saline or cocaine injection (15 mg/kg, i.p.) for 5 d. After 7 d of withdrawal from injections, rats were challenged with cocaine during functional imaging. Acute cocaine administration produced positive BOLD activation in the prefrontal cortex, nucleus accumbens, striatum, ventral tegmental area, and hippocampus, among other brain regions. Positive BOLD signal changes were lower in Ovx+E than in Ovx rats. With repeated cocaine administration, Ovx+E rats showed enhanced BOLD signal changes in the nucleus accumbens, ventral tegmental area, and hippocampus compared with acutely treated animals. Our results indicate that estrogen influences the effects of acute and repeated cocaine administration on BOLD signal changes. The data suggest that in females with estrogen, cocaine-induced neuronal activity is enhanced after repeated cocaine administration. It is possible that the actions of estrogen within the aforementioned brain regions potentiate the behavioral response to cocaine observed in female rats

Vasopressin-dependent flank marking in golden hamsters is suppressed by drugs used in the treatment of obsessive-compulsive disorder

BACKGROUND: Alterations in arginine vasopressin regulation and secretion have been proposed as one possible biochemical abnormality in patients with obsessive-compulsive disorder. In golden hamsters, arginine vasopressin microinjections into the anterior hypothalamus trigger robust grooming and flank marking, a stereotyped scent marking behaviors. The intensity and repetition of the behaviors induced by arginine vasopressin is somewhat reminiscent of Obsessive Compulsive Disorder in humans. The present experiments were carried out to test whether pharmacological agents used to alleviate obsessive compulsive disorder could inhibit arginine vasopressin-induced flank marking and grooming. RESULTS: Male golden hamsters were treated daily for two weeks with either vehicle, fluoxetine, clomipramine, or desipramine (an ineffective drug), before being tested for arginine vasopressin-induced flank marking and grooming. Flank marking was significantly inhibited in animals treated with fluoxetine or clomipramine but unaffected by treatment with desipramine. Grooming behavior was not affected by any treatment. CONCLUSION: These data suggest that arginine vasopressin-induced flank marking may serve as an animal model for screening drugs used in the control of Obsessive Compulsive Disorder

Vasopressin/serotonin interactions in the anterior hypothalamus control aggressive behavior in golden hamsters

Studies in several species of rodents show that arginine vasopressin (AVP) acting through a V1A receptor facilitates offensive aggression, i.e., the initiation of attacks and bites, whereas serotonin (5-HT) acting through a 5-HT1B receptor inhibits aggressive responding. One area of the CNS that seems critical for the organization of aggressive behavior is the basolateral hypothalamus, particularly the anterior hypothalamic region. The present studies examine the neuroanatomical and neurochemical interaction between AVP and 5-HT at the level of the anterior hypothalamus (AH) in the control of offensive aggression in Syrian golden hamsters. First, specific V1A and 5-HT1B binding sites in the AH are shown by in vitro receptor autoradiography. The binding for each neurotransmitter colocalizes with a dense field of immunoreactive AVP and 5-HT fibers and putative terminals. Putative 5-HT synapses on AVP neurons in the area of the AH are identified by double-staining immunocytochemistry and laser scanning confocal microscopy. These morphological data predispose a functional interaction between AVP and 5-HT at the level of the AH. When tested for offensive aggression in a resident/intruder paradigm, resident hamsters treated with fluoxetine, a selective 5-HT reuptake inhibitor, have significantly longer latencies to bite and bite fewer times than vehicle-treated controls. Conversely, AVP microinjections into the AH significantly shorten the latency to bite and increase biting attacks. The action of microinjected AVP to increase offensive aggression is blocked by the pretreatment of hamsters with fluoxetine. These data suggest that 5-HT inhibits fighting, in part, by antagonizing the aggression-promoting action of the AVP system

Novel Magnetic Resonance Imaging strategy targeting Neurotensin Receptors in detection of Prostate Cancer [preprint]

Prostate cancer is the second leading cause of all male cancer deaths. One of the factors present in malignant prostate cells and shown to support its metastatic growth is the neuropeptide neurotensin (NT). The primary goal of the present study was to establish the feasibility of using a newly developed paramagnetic receptor ligand for NT and non-invasive ultrahigh-field magnetic resonance (MR) imaging to visualize prostate cancer in rodents. Orthotropic xenografts were initiated in six-week old male BALB/c nu/nu athymic mice (n = 28) by intra-prostatic (ventral lobe) inoculation of human prostate cancer cells (10 μL of PC3 cells (10^6/100 μL)). Palpable tumors developed within 30-60 days. A micro-imager utilized in these studies was an actively shielded 9.4T, 89 mm bore, Oxford superconducting magnet with a 100 gauss/cm gradient system. Prior to contrast injection, T2 weighted anatomy scans were done to localize the tumor with a spin-echo multi-slice sequence with TR: 2000 TE: 40 and NEX: 1 in both coronal and axial planes. The paramagnetic ligand data sets were collected with a spin-echo, T1 weighted pulse sequence (MSME): TR 300 msec; TE 5 msec; NEX 4 in both axial and coronal planes. The data sets were taken initially at 5-min intervals post contrast injection for the first half hour and then at 15 min intervals for the next 1.5-2 hours for a time series analyses. The temporal distribution of MR signal intensity in various regions were determined in the absence and presence of NT. Our results confirm that the novel NT molecule was protected from enzymatic degradation and capable of forming a high-affinity paramagnetic NT ligand with an extended half-life. During the imaging studies, the signal intensity increased by 200% in the region of the tumor. This increase in signal intensity approached maximum binding within 30 minutes and remained visible for 1-hour post-injection of the contrast agent. Taken together, these findings suggest that it is feasible to detect and image prostate cancer using a paramagnetic NT ligand and the emergence of the NT receptor ligand that may be used as a diagnostic marker for prostate cancer in humans

Cardioacceleration in alloparents in response to stimuli from prairie vole pups: The significance of thermoregulation

Autonomic responses, including changes in heart rate and respiratory sinus arrhythmia (RSA) can provide indications of emotional reactivity to social stimuli in mammals. We have previously reported that male prairie voles (Microtus ochrogaster) spontaneously care for unfamiliar infants, showing a robust and sustained increase in heart rate in the presence of a pup, thus providing an opportunity to examine the physiology of care-giving in reproductively naïve animals. However, the purpose of such heart rate increases has not been explained by previous efforts. In the present study, we first compared male and female prairie vole cardiac responses in the presence of a pup and found no evidence of sex differences in heart rate or RSA. Using male prairie voles, we then examined the characteristics of pups that were capable of eliciting physiological responses, including age of the pup and pup odors. As prairie vole pups increased in age they vocalized less and there was an associated decline in alloparental cardioacceleration. Exposure to pup-related odors induced cardioacceleration in adult males and this effect also diminished with increasing pup age. Finally, we were able to block the cardioacceleratory effect when the testing environment was warmed to a temperature of 36° C [versus ambient room temperature (approximately 22° C)]. These findings suggest that pup-induced cardioacceleration is a robust phenomenon across alloparental prairie voles of both sexes, and depends on multi-modal processing of different stimuli from the pups. Young pups require care-giving behavior, which appears to drive cardioacceleration in the alloparent. This study also supports the usefulness of autonomic measures in the evaluation of social experiences

TB STIGMA – MEASUREMENT GUIDANCE

TB is the most deadly infectious disease in the world, and stigma continues to play a significant role in worsening the epidemic. Stigma and discrimination not only stop people from seeking care but also make it more difficult for those on treatment to continue, both of which make the disease more difficult to treat in the long-term and mean those infected are more likely to transmit the disease to those around them. TB Stigma – Measurement Guidance is a manual to help generate enough information about stigma issues to design and monitor and evaluate efforts to reduce TB stigma. It can help in planning TB stigma baseline measurements and monitoring trends to capture the outcomes of TB stigma reduction efforts. This manual is designed for health workers, professional or management staff, people who advocate for those with TB, and all who need to understand and respond to TB stigma