Repeated subcutaneous administration of PT150 has dose-dependent effects on sign tracking in male Japanese quail.

Rice, Beth Ann; Saunders, Meredith A.; Jagielo-Miller, Julia E.; Prendergast, Mark A.; Akins, Chana K.

doi:10.1037/pha0000275

Cited by 12 publications

(16 citation statements)

References 32 publications

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“…Further, lesions of the ventral, but not the dorsal, hippocampus decrease the propensity to sign-track ( Fitzpatrick et al, 2016 ). While it is remains to be determined whether these lesion effects are dependent on GR function, it should be noted that systemic administration of a GR antagonist similarly attenuates the acquisition of sign-tracking behavior ( Rice et al, 2018 , 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Male Goal-Tracker and Sign-Tracker Rats Do Not Differ in Neuroendocrine or Behavioral Measures of Stress Reactivity

Lopez¹,

Mubarak

Yang

et al. 2021

eNeuro

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Section: Discussionmentioning

confidence: 99%

Male Goal-Tracker and Sign-Tracker Rats Do Not Differ in Neuroendocrine or Behavioral Measures of Stress Reactivity

Lopez¹,

Mubarak

Yang

et al. 2021

eNeuro

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“…However, higher dosing would be necessary to specify if an actual CC50, if any cytotoxicity can be identified. As already noted, no significant cytotoxicities were identified in the compound's extensive pre-clinical and clinical (phase 1, 2) studies [6,[13][14][15][16][17][18].…”

Section: Discussionmentioning

confidence: 99%

Clinical stage molecule PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2.

et al. 2020

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PT150 is a clinical-stage molecule, taken orally, with a strong safety profile having completed Phase 1 and Phase 2 clinical trials for its original use as an antidepressant. It has an active IND for COVID-19. Antiviral activities have been found for PT150 and other members of its class in a variety of virus families; thus, it was now tested against SARS-CoV-2 in human bronchial epithelial lining cells and showed effective 90% inhibitory antiviral concentration (EC90) of 5.55 µM. PT150 is a member of an extended platform of novel glucocorticoid receptor (GR) and androgen receptor (AR) modulating molecules. In vivo, their predominant net effect is one of systemic glucocorticoid antagonism, but they also show direct downregulation of AR and minor GR agonism at the cellular level. We hypothesize that anti-SARS-CoV-2 activity depends in part on this AR downregulation through diminished TMPRSS2 expression and modulation of ACE2 activity. Given that hypercortisolemia is now suggested to be a significant co-factor for COVID-19 progression, we also postulate an additive role for its potent immunomodulatory effects through systemic antagonism of cortisol.

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“…In support, lesions of the ventral, but not the dorsal, hippocampus decrease the propensity to sign-track (Fitzpatrick et al, 2016). While it is remains to be determined whether these lesion effects are dependent on GR function, it should be noted that systemic administration of a GR antagonist similarly attenuates the acquisition of sign-tracking behavior (Rice et al, 2018; Rice et al, 2019). Taken together, GR function, and presumably that within the ventral hippocampus, appears to play an important role in incentive motivational processes.…”

Section: Discussionmentioning

confidence: 99%

Neuroendocrine and behavioral measures of stress-reactivity in male goal-tracker and sign-tracker rats

Lopez

Mubarak

Yang

et al. 2020

Preprint

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Cues, or stimuli in the environment, attain the ability to guide behavior via learned associations. As predictors, cues can elicit adaptive behavior and lead to valuable resources (e.g., food). For some individuals, however, cues are transformed into incentive stimuli and can elicit maladaptive behavior. The goal-tracker/sign-tracker animal model captures individual differences in cue-motivated behaviors, with reward-associated cues serving as predictors of reward for both goal-trackers and sign-trackers, but becoming incentive stimuli only for sign-trackers. While these distinct phenotypes are characterized based on Pavlovian conditioned approach behavior, they exhibit differences on a number of behaviors of relevance to psychopathology. To further characterize the neurobehavioral endophenotype associated with individual differences in cue-reward learning, we investigated neuroendocrine and behavioral profiles associated with negative valence in male goal-trackers, sign-trackers, and intermediate responders. We found that baseline corticosterone increases with Pavlovian learning, and that this increase is positively associated with the development of sign-tracking. We did not observe significant differences between goal-trackers and sign-trackers in behavior during an elevated plus maze or open field test, nor did we see differences in the corticosterone response to the open field test or physiological restraint. We did, however, find that sign-trackers have greater glucocorticoid receptor mRNA expression in the ventral hippocampus, with no phenotypic differences in the dorsal hippocampus. These findings suggest that goal-trackers and sign-trackers do not differ on indices of negative valence; rather, differences in neuroendocrine measures between these phenotypes can be attributed to distinct cue-reward learning styles.

show abstract

Repeated subcutaneous administration of PT150 has dose-dependent effects on sign tracking in male Japanese quail.

Cited by 12 publications

References 32 publications

Male Goal-Tracker and Sign-Tracker Rats Do Not Differ in Neuroendocrine or Behavioral Measures of Stress Reactivity

Male Goal-Tracker and Sign-Tracker Rats Do Not Differ in Neuroendocrine or Behavioral Measures of Stress Reactivity

Clinical stage molecule PT150 is a modulator of glucocorticoid and androgen receptors with antiviral activity against SARS-CoV-2.

Neuroendocrine and behavioral measures of stress-reactivity in male goal-tracker and sign-tracker rats

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