Sex-specific effects of psychedelics on prepulse inhibition of startle in 129S6/SvEv mice

Vohra, Hiba Z.; Saunders, Justin M.; Jaster, Alaina M; Revenga, Mario de la Fuente; Jimenez, Jennifer; Fernández-Teruel, Alberto; Wolstenholme, Jennifer T.; Beardsley, Patrick M.; González-Maeso, Javier

doi:10.1007/s00213-021-05913-9

Cited by 12 publications

(3 citation statements)

References 62 publications

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“…In addition, psychedelic compounds are known to have differing effects in male and female rodents. Female rats are less sensitive to locomotor and thigmotaxis-related effects of LSD (Páleníček et al, 2010), and sex appears to contribute on the disruption of pre-pulse inhibition by psychedelics both in rats and mice (Páleníček et al, 2010; Vohra et al, 2021). Furthermore, while an example of a different drug class, the glutamate N-methyl-D-aspartate receptor inhibitor ketamine might affect ethanol binge drinking differently in male and female mice (Crowley et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Effects of acute lysergic acid diethylamide on intermittent ethanol and sucrose drinking and intracranial self-stimulation in C57BL/6 mice

et al. 2022

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Background: Psychedelics, like lysergic acid diethylamide (LSD), are again being studied as potential therapies for many neuropsychiatric disorders, including addictions. At the same time, the acute effects of psychedelics on rewarding behaviours have been scarcely studied. Aims: The current study aimed to clarify if LSD decreases binge-like ethanol drinking in mice, and whether the observed acute effects on ethanol consumption are generalizable to a natural reinforcer, sucrose, and if the effects resulted from aversive or reward-attenuating effects caused by LSD. Methods: The effects of acute LSD were examined using 2-bottle choice intermittent ethanol (20%) and sucrose drinking (10%), discrete-trial current-intensity threshold method of intracranial self-stimulation and short-term feeding behaviour assay in C57BL/6 male mice. Results: The results showed that acute 0.1 mg/kg, but not 0.05 mg/kg, dose (i.p.) of LSD reduced 2-h intermittent ethanol drinking transiently without any prolonged effects. No effects were seen in intermittent 2-h sucrose drinking. The tested LSD doses had neither effect on the intracranial self-stimulation current-intensity thresholds, nor did LSD affect the threshold-lowering, or rewarding, effects of simultaneous amphetamine treatment. Furthermore, LSD had small, acute diminishing effects on 2-h food and water intake. Conclusions: Based on these results, LSD decreases binge-like ethanol drinking in mice, but only acutely. This effect is not likely to stem from reward-attenuating effects but could be in part due to reduced consummatory behaviour.

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Section: Discussionmentioning

confidence: 99%

Effects of acute lysergic acid diethylamide on intermittent ethanol and sucrose drinking and intracranial self-stimulation in C57BL/6 mice

et al. 2022

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“…In humans, sex is not predictive of the effects or optimal dosing of psychedelics including LSD (56). However, in rats there is some evidence that LSD and other psychedelics have slightly different behavioral effects in males and females (57,58). Thus, future work should continue to include both sexes and when possible be powered to compare between sexes directly.…”

Section: Discussionmentioning

confidence: 99%

Lysergic Acid Diethylamide Alters the Effects of Brain Stimulation in Rodents

Dwiel

Henricks

Bragg

et al. 2022

Preprint

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Background: Psychedelics have resurged in neuroscience and psychiatry with promising success in psychedelic-assisted therapy for the treatment of anxiety, depression, and addiction. At the cellular level, psychedelics elicit neuroplastic processes 24 hours after administration, priming neural circuits for change. The acute effects of psychedelics are well characterized with functional imaging and neural oscillations showing an increase in the entropy of spontaneous cortical activity. Hypotheses: We hypothesized that cortical-striatal oscillations recorded in rats would confirm the effects of psychedelics. We also hypothesized that brain stimulation delivered 24 hours after LSD administration would lead to different effects than brain stimulation alone. Methods: We recorded local field potential (LFP) oscillations from rats following lysergic acid diethylamide (LSD) or saline administration and determined if exposure to these treatments altered the effect of a targeted intervention (brain stimulation) 24 hours later. Results: We confirmed acutely decreased low frequency power across the brain when rats are given LSD. We also demonstrated these altered states return to baseline after 24 hours. Brain stimulation applied in this window of heightened neuroplasticity produced distinct shifts in brain state compared to brain stimulation applied 24 hours after saline. Conclusions: Despite the acute effects of LSD disappearing after 24 hours, there are still latent effects that synergize with brain stimulation to create different changes in brain activity compared to brain stimulation alone. Our findings are the first to suggest that psychedelics could have a role clinically in combination with brain stimulation to achieve enhanced effects on brain activity and clinical outcomes.

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“…PPI of startle experiments were conducted following a previously described paradigm ( 71 ). Briefly, mice were placed in SR-Lab Startle Response System (San Diego Instruments) chambers and allowed to habituate to background noise for 5 min.…”

Section: Methodsmentioning

confidence: 99%

Glucocorticoid receptor dysregulation underlies 5-HT2AR-dependent synaptic and behavioral deficits in a mouse neurodevelopmental disorder model

Saunders¹,

Muguruza²,

Sierra³

et al. 2022

Journal of Biological Chemistry

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Sex-specific effects of psychedelics on prepulse inhibition of startle in 129S6/SvEv mice

Cited by 12 publications

References 62 publications

Effects of acute lysergic acid diethylamide on intermittent ethanol and sucrose drinking and intracranial self-stimulation in C57BL/6 mice

Effects of acute lysergic acid diethylamide on intermittent ethanol and sucrose drinking and intracranial self-stimulation in C57BL/6 mice

Lysergic Acid Diethylamide Alters the Effects of Brain Stimulation in Rodents

Glucocorticoid receptor dysregulation underlies 5-HT2AR-dependent synaptic and behavioral deficits in a mouse neurodevelopmental disorder model

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