Neuroplasticity: The Continuum of Change.

Neuroplasticity is a term that is increasingly permeating mainstream discourse and being used by the popular press to simplify descriptions of how the brain changes in response to stimuli such as exercise, sleep, food, drugs of abuse, and medicines, among others. However, it is a complex, multifaceted concept representing a continuum connecting molecular, cellular, and circuit-level changes and their effects on human behavior. In this Viewpoint, we examine neuroplasticity from several perspectives to construct a holistic view of this ambiguous term. By engaging experts across various scientific disciplines, we attempt to provide an easy entry point to the concept of neuroplasticity for readers of ACS Chemical Neuroscience. By highlighting how neuroplasticity changes in both health and disease, we demonstrate that the concept is applicable to both adaptive and maladaptive responses to stimuli, underscoring its significance in chemical neuroscience.

Psychedelic-inspired drug discovery using an engineered biosensor.

Ligands can induce G protein-coupled receptors (GPCRs) to adopt a myriad of conformations, many of which play critical roles in determining the activation of specific signaling cascades associated with distinct functional and behavioral consequences. For example, the 5-hydroxytryptamine 2A receptor (5-HT2AR) is the target of classic hallucinogens, atypical antipsychotics, and psychoplastogens. However, currently available methods are inadequate for directly assessing 5-HT2AR conformation both in vitro and in vivo. Here, we developed psychLight, a genetically encoded fluorescent sensor based on the 5-HT2AR structure. PsychLight detects behaviorally relevant serotonin release and correctly predicts the hallucinogenic behavioral effects of structurally similar 5-HT2AR ligands. We further used psychLight to identify a non-hallucinogenic psychedelic analog, which produced rapid-onset and long-lasting antidepressant-like effects after a single administration. The advent of psychLight will enable in vivo detection of serotonin dynamics, early identification of designer drugs of abuse, and the development of 5-HT2AR-dependent non-hallucinogenic therapeutics.

Dark Classics in Chemical Neuroscience: N, N-Dimethyltryptamine (DMT).

Though relatively obscure, N, N-dimethyltryptamine (DMT) is an important molecule in psychopharmacology as it is the archetype for all indole-containing serotonergic psychedelics. Its structure can be found embedded within those of better-known molecules such as lysergic acid diethylamide (LSD) and psilocybin. Unlike the latter two compounds, DMT is ubiquitous, being produced by a wide variety of plant and animal species. It is one of the principal psychoactive components of ayahuasca, a tisane made from various plant sources that has been used for centuries. Furthermore, DMT is one of the few psychedelic compounds produced endogenously by mammals, and its biological function in human physiology remains a mystery. In this review, we cover the synthesis of DMT as well as its pharmacology, metabolism, adverse effects, and potential use in medicine. Finally, we discuss the history of DMT in chemical neuroscience and why this underappreciated molecule is so important to the field of psychedelic science.

Radiographic comparison of three methods for nasal saline irrigation.

OBJECTIVE: To compare intranasal distribution of saline solution delivered by three popular methods for nasal saline irrigation. STUDY DESIGN: Prospective, controlled comparison. METHODS: Eight healthy adult volunteers received nasal irrigation with 40 mL of isotonic, nonionic contrast material immediately before having coronal computed tomography to visualize distribution of solution in the paranasal sinuses. For each study subject, three methods of irrigation were used: irrigation using positive-pressure irrigation, irrigation using negative-pressure irrigation, and irrigation using a nebulizer. For each subject, three-dimensional computer reconstructions of the irrigated paranasal sinus airspaces were used to compare contrast solution volume and distribution achieved by the three methods. RESULTS: Of the three methods used, two methods, positive-pressure and negative-pressure irrigation, distributed contrast solution widely to ethmoid and maxillary sinuses, but distribution of contrast solution was more uniform using positive-pressure irrigation than using negative-pressure irrigation. The nebulization method distributed contrast solution poorly and resulted in a significantly lower volume of retained contrast solution (P <.05). CONCLUSION: Judged solely on the basis of solution distribution in the nasal sinuses, nasal irrigation is effective when either positive-pressure or negative-pressure irrigation is used but is ineffective when a nebulizer is used.