Oxytocin and Serotonin Brain Mechanisms in the Nonhuman Primate.

Oxytocin (OT) is increasingly studied for its therapeutic potential in psychiatric disorders, which are associated with the deregulation of several neurotransmission systems. Studies in rodents demonstrated that the interaction between OT and serotonin (5-HT) is critical for several aspects of social behavior. Using PET scan in humans, we have recently found that 5-HT 1A receptor (5-HT1AR) function is modified after intranasal oxytocin intake. However, the underlying mechanism between OT and 5-HT remains unclear. To understand this interaction, we tested 3 male macaque monkeys using both [11C]DASB and [18F]MPPF, two PET radiotracers, marking the serotonin transporter and the 5-HT1AR, respectively. Oxytocin (1 IU in 20 µl of ACSF) or placebo was injected into the brain lateral ventricle 45 min before scans. Additionally, we performed postmortem autoradiography. Compared with placebo, OT significantly reduced [11C]DASB binding potential in right amygdala, insula, and hippocampus, whereas [18F]MPPF binding potential increased in right amygdala and insula. Autoradiography revealed that [11C]DASB was sensitive to physiological levels of 5-HT modification, and that OT does not act directly on the 5-HT1AR. Our results show that oxytocin administration in nonhuman primates influences serotoninergic neurotransmission via at least two ways: (1) by provoking a release of serotonin in key limbic regions; and (2) by increasing the availability of 5-HT1AR receptors in the same limbic areas. Because these two molecules are important for social behavior, our study sheds light on the specific nature of their interaction, therefore helping to develop new mechanisms-based therapies for psychiatric disorders.SIGNIFICANCE STATEMENT Social behavior is largely controlled by brain neuromodulators, such as oxytocin and serotonin. While these are currently targeted in the context of psychiatric disorders such as autism and schizophrenia, a new promising pharmaceutical strategy is to study the interaction between these systems. Here we depict the interplay between oxytocin and serotonin in the nonhuman primate brain. We found that oxytocin provokes the release of serotonin, which in turn impacts on the serotonin 1A receptor system, by modulating its availability. This happens in several key brain regions for social behavior, such as the amygdala and insula. This novel finding can open ways to advance treatments where drugs are combined to influence several neurotransmission networks.

Two functions of the primate amygdala in social gaze.

Appropriate gaze interaction is essential for primate social life. Prior studies have suggested the involvement of the amygdala in processing eye cues but its role in gaze behavior during live social exchanges remains unknown. We recorded the activity of neurons in the amygdala of two monkeys as they engaged in spontaneous visual interactions. We showed that monkeys adjust their oculomotor behavior and actively seek to interact with each other through mutual gaze. During fixations on the eye region, some amygdala neurons responded with short latency and more strongly to mutual than non-reciprocal gaze (averted gaze). Other neurons responded with long latency and were more strongly modulated by active, self-terminated mutual gaze fixations than by passively terminated ones. These results suggest that the amygdala not only participates to the evaluation of eye contact, but also plays a role in the timing of fixations which is crucial for adaptive social interactions through gaze.

Efficacy of alum for treatment of recurrent aphthous stomatitis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is the most common painful ulcers of oral mucosal which can cause many sufferings. Treatment of RAS often includes administration of corticosteroids, analgesics and regulators of the immune system. However, considering the side effects of these medications, even their topical application must be done with caution. Alum is used in traditional medicine for treatment of oral ulcers without significant side effect. This study sought to assess the effect of topical application of alum on aphthous ulcers. METHODS: This clinical randomized double-blind placebo-controlled study was conducted on 50 females aged 21 to 27 years. Mucosal adhesive patches were prepared in two forms of basic and 7% alum-containing patches. Subjects in two groups of case and control randomly received the mucosal adhesive patches containing alum and the basic patches, respectively three times in five days. Duration of recovery, changes in size of lesion and severity of pain were recorded. Data were entered into SPSS Version 16 and analyzed using t-test. RESULTS: The average period of full recovery was 7.52 days in the case and 12.2 days in the control groups; which was significantly different (p<0.001). Size of wound and severity of pain were significantly lower at one, three and five days posttreatment compared to baseline values before treatment in the case group (p<0.001) and the difference in this regard between the case and control groups was statistically significant. CONCLUSION: Alum can significantly decrease the size of aphthous lesions, severity of pain and expedite the recovery of patients with RAS.

Levels of salivary antioxidant vitamins and lipid peroxidation in patients with oral lichen planus and healthy individuals.

Oral lichen planus (OLP) is a chronic inflammatory mucosal disease of unknown etiology. Many studies have implicated the protective role of antioxidants in such diseases. The aim of this study was to compare salivary total antioxidant capacity (TAC and malondialdehyde (MDA) and antioxidant vitamin (vitamin s A, C and E) levels in patients with erosive OLP and healthy individuals. Thirty six patients with OLP (14 males, 22 females) and 36 control subjects (15 males, 21 females), matched for age and sex were enrolled in this case control study. The salivary levels of MDA, TAC, and antioxidant vitamin levels were measured in both case and control groups. The salivary level of MDA was significantly higher (p<0.001) in patients than in controls. In patients with OLP, the TAC of saliva was significantly lower than that in healthy subjects (p<0.001). Compared with controls, the levels of salivary antioxidant vitamins were significantly decreased in patients with OLP (p<0.001). In addition, a positive correlation was found between the decrease in the salivary amount of vitamin C and that in vitamin E in patients and controls. In addition to the lower salivary levels of antioxidant vitamins and the lower TAC, the higher level of MDA in patients with OLP suggests that free radicals and the resulting oxidative damage may be important in the pathogenesis of OLP lesions.