Signaling Mechanism Responsible for 5-HT2A Receptor Tolerance to Psychedelic Induced Head-Twitch Behavior in Mice

In recent years, there has been a growing interest in psychedelic compounds stemming from their promising use as therapeutic agents and research tools that can be used to treat and study several neuropsychiatric disorders. Psychedelics have proven useful in a broad range of these diseases - they serve as models for psychosis in schizophrenia but have also had promising results in treating major depressive disorder, anxiety, and other common disorders. Decreased stigmatization surrounding psychedelics has further increased their use in research and clinical settings. In light of these trends and the promising nature of their use, a thorough understanding of the mechanisms underlying their action is necessary. The Serotonin 2A Receptor, or 5-HT2AR, has been shown to play a major role in neuropsychiatric disorders and also serves as the primary receptor mediating psychedelic action. In rodent models, administration of psychedelics such as the phenethylamine-derived compound 2,5-dimethoxy-4-iodoamphetamine (DOI) produces a behavior known as the head twitch response. This characteristic head movement occurs as the specific result of 5-HT2AR activation by psychedelic substances and in tandem with characteristic psychedelic genotypic expression pathways, and can, therefore, be used to quantify 5-HT2AR activation. Repeated administration of psychedelics has also been shown to lead to tolerance, producing diminished therapeutic effects for otherwise promising treatments. In animal models, tolerance can be demonstrated using the HTR model, quantified through progressive decreases in the number of head twitch behaviors elicited upon psychedelic administration. While several theories have attempted to explain the mechanisms behind tolerance, they remain unknown and are worthy of further study. My project aimed to examine signaling pathways underlying psychedelic action, the head twitch response, and tolerance in order to more fully understand the mechanisms behind these processes. My results indicate that the Mitogen-Activated Protein Kinase, ERK, plays a role in mediating the head twitch response acutely, highlighting this signaling pathway as a mediator of this behavioral response. However, signaling blockade at the level of ERK failed to prevent tolerance development. Interestingly, signaling blockade at the level of Protein Kinase C (PKC) failed to diminish head twitch acutely and also failed to prevent tolerance. Finally, pre-treatment with the 5-HT2AR specific antagonist M100,907 attenuated head twitch acutely but similarly failed to prevent tolerance. Collectively, these results point towards the MAP Kinase pathway as important in mediating psychedelic induced head twitch behavior, but further study is needed to investigate the source of tolerance

Spin-flip and spin-conserving optical transitions of the nitrogen-vacancy centre in diamond

We map out the first excited state sublevel structure of single nitrogen-vacancy (NV) colour centres in diamond. The excited state is an orbital doublet where one branch supports an efficient cycling transition, while the other can simultaneously support fully allowed optical Raman spin-flip transitions. This is crucial for the success of many recently proposed quantum information applications of the NV defects. We further find that an external electric field can be used to completely control the optical properties of a single centre. Finally, a group theoretical model is developed that explains the observations and provides good physical understanding of the excited state structure

Age and adult attachment style predict psychological distress in the Singapore general population during COVID-19

To date, there is increasing evidence to suggest that age and adult attachment styles, such as secure, anxious and avoidant attachment are predictive or protective for psychological distress. The study aimed to investigate the extent to which age and adult attachment style, measured by the Attachment Style Questionnaire, predicted psychological distress, measured by the Kessler 10 Psychological Distress Scale, in the Singapore general population during COVID-19. Ninety-nine residents of Singapore (44 females, 52 males, 3 prefer not to state their gender) aged between 18 and 66 completed an online survey, which collected information on age, adult attachment styles and levels of psychological distress. Multiple regression analysis was performed to study the influence of predictive factors on psychological distress. The study identified 20.2%, 13.1% and 14.1% of participants reporting psychological distress at the mild, moderate and severe levels, respectively. The study also reported that age and psychological distress were negatively correlated, and that psychological distress was negatively correlated with both anxious and avoidant attachment styles. It was concluded that age and adult attachment style significantly predicted psychological distress in the Singapore general population during COVID-19. Further studies exploring other variables and risk factors are required to further consolidate these results. At the global level, these findings may help countries predict residents' reactions to future outbreaks and help them prepare strategies and approaches to address these situations

Low temperature studies of the excited-state structure of Nitrogen-Vacancy color centers in diamond

We report a study of the 3E excited-state structure of single nitrogen-vacancy (NV) defects in diamond, combining resonant excitation at cryogenic temperatures and optically detected magnetic resonance. A theoretical model of the excited-state structure is developed and shows excellent agreement with experimental observations. Besides, we show that the two orbital branches associated with the 3E excited-state are averaged when operating at room temperature. This study leads to an improved physical understanding of the NV defect electronic structure, which is invaluable for the development of diamond-based quantum information processing.Comment: 4 pages, 4 figure