Shelby A McGriff, Jacquelin C Hecker, Alexander D Maitland, John S Partilla, Michael H Baumann, Grant C Glatfelter
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引用次数: 0
Abstract
Rationale: The head twitch response (HTR) is a spontaneously occurring behavior in mice that is increased in frequency by serotonergic psychedelics. The mouse HTR is often used as a proxy for psychedelic-like drug effects, but limited information is available about sex differences in HTRs evoked by various classes of psychedelics (i.e., phenethylamines, lysergamides, tryptamines).
Objective and methods: To examine potential sex differences in responsiveness to structurally-distinct psychedelics, acute effects of subcutaneous 2,5-dimethoxy-4-iodo-amphetamine (DOI, 0.03-10 mg/kg), lysergic acid diethylamide (LSD, 0.003-1 mg/kg), and 4-phosphoryloxy-N,N-dimethyltryptamine (psilocybin, 0.03-10 mg/kg) on HTRs were compared in male and female C57BL/6J mice. For comparison, effects of the drugs on locomotor activity and body temperature were also determined.
Results: Drug potencies for inducing HTRs were similar in males and females for all drugs, with only LSD exhibiting detectable differences due to increased maximal counts in females. Importantly, the maximum number of HTRs observed for all drugs was higher in females, with significant differences between sexes for DOI and LSD. Dose x sex interactions for the dose-response data were statistically significant for psilocybin and LSD, with females displaying more HTRs after the highest or peak doses of all drugs. The acute effects of drugs on locomotion and temperature varied by drug, but were similar in both sexes.
Conclusions: The present results overall show no substantial sex differences in the potencies to induce HTRs for DOI, LSD, and psilocybin in C57BL/6J mice. However, females uniformly displayed more HTRs at high doses administered across chemotypes. The results further suggest that commonly used doses of psychedelics induce comparable psychedelic-like effects in male and female C57BL/6J mice, but modest differences may emerge at high doses.
期刊介绍：
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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