Biology subjects

Bray, E.

Publications and source records attributed to Bray, E..

3 recordsLinked to original sources

bioRxiv2026

Serotonergic Polypharmacology of 2-Halogenated Tryptamines

Serotonergic psychedelics such as N,N-dimethyltryptamine (DMT) and 4-phosphoryloxy-N,N-dimethyltryptamine (psilocybin) show therapeutic promise for psychiatric and neurodegenerative disorders but may be limited by liabilities from serotonin (5-HT)-2A mediated psychoactive effects and potential cardiotoxicity via 5-HT2B activation. To address these limitations, we designed and synthesized 2-halogenated derivatives of DMT and psilacetin to reduce 5-HT2A/5-HT2B activity while retaining engagement of therapeutically relevant targets, particularly 5-HT6, 5-HT2C, and 5-HT1B. This study demonstrated that 2-position halogenation decreased affinities, potencies, and efficacies at 5-HT2A and 5-HT1A receptors while preserving potent 5-HT6 agonism, especially for 2-Br-psilocin. The analogues exhibited reduced affinities at 5-HT2B and hERG ion channels, suggesting safer cardiac valve and cardiotoxic profiles. In C57BL/6J mice, 2-Br-psilacetin did not induce the head-twitch response and attenuated 2,5 dimethoxy-4-iodoamphetamine (DOI)-induced head-twitch behavior, suggesting a reduced potential for inducing psychedelic effects. Behavioral assays further revealed improvements in stress-induced affective measures and hippocampus-independent cued learning at intermediate doses. These findings identify 2-halogenated tryptamines as polypharmacological serotonergic ligands with reduced psychoactivity and cardiac valve and toxic liabilities, supporting their potential as next-generation psychedelic-inspired therapeutics. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=86 SRC="FIGDIR/small/718915v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@17975a5org.highwire.dtl.DTLVardef@11ae1f1org.highwire.dtl.DTLVardef@1e7a00aorg.highwire.dtl.DTLVardef@1bbfcc8_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2024

Longitudinal evidence for the emergence of multiple intelligences in assistance dog puppies

Cognitive test batteries suggest that adult dogs have different types of cognitive abilities that vary independently. In the current study, we tested puppies repeatedly over a crucial period of development to explore the timing and rate at which these different cognitive skills develop. Service dog puppies (n = 113), raised using two different socialization strategies, were either tested longitudinally (n =91) or at a single time point (n = 22). Subjects tested longitudinally participated in the battery every two weeks during and just beyond their final period of rapid brain growth (from approximately 8-20 weeks of age). Control puppies only participated in the test battery once, which allowed us to evaluate the impact of repeated testing. In support of the multiple intelligences hypothesis (MIH), cognitive skills emerged at different points across the testing period, not simultaneously. Maturational patterns also varied between cognitive skills, with puppies showing adult-like performance on some tasks only weeks after a skill emerged, while never achieving adult performance in others. Differences in rearing strategy did not lead to differences in developmental patterns while, in some cases, repeated testing did. Overall, our findings provide strong support for the MIH by demonstrating differentiated development across the cognitive abilities tested.

animal behavior and cognition↗

bioRxiv2021

Cooperative Communication with Humans Evolved to Emerge Early in Dogs

While we know that dogs evolved from wolves through a process of domestication, it remains unclear how this process may have affected dog cognitive development. Here we tested dog (N=44) and wolf (N=37) puppies, 5-18 weeks old, on a battery of temperament and cognition tasks. Dog puppies were more attracted to humans, read human gestures more skillfully and made more eye contact with humans than wolf puppies. The two species were similarly attracted to objects and performed similarly on nonsocial measures of memory and inhibitory control. These results demonstrate the role of domestication in enhancing the cooperative communication skills of dogs through selection on attraction to humans, which altered developmental pathways. One Sentence Summary Domestication altered dogs developmental pathways to enhance their cooperative communication with humans.

animal behavior and cognition↗