A glucocorticoid receptor antagonist reduces sign-tracking behavior in male Japanese quail.

Abstract

Addiction is characterized as a chronic debilitating disease. One devastating feature of addiction is the susceptibility of relapse (40-60%) after stretches of abstinence. One theory that may account for relapse suggests that drug cues (e.g., paraphernalia) may increase stress hormones, and this may prompt relapse. Repeatedly pairing a neutral cue with a reward is commonly utilized to measure what subjects learn about a cue that is predictive of reward. Research has shown that animals that attend to a cue more than to the reward (sign trackers) may be more vulnerable to drug addiction. Additionally, research has shown that sign tracking is associated with an increase in corticosterone, a primary stress hormone. PT150 is a novel glucocorticoid receptor antagonist that moderates the release of corticosterone. In the current experiment, it was hypothesized that subjects given repeated administration of PT150 would reduce sign tracking compared to subjects given placebo. Time spent (in seconds) near a cue that predicts reward (conditional stimulus) served as a measure of sign tracking, and PT150 or placebo was administered following sign tracking. An independent-samples t test revealed that subjects that received PT150 had reduced time spent near the conditioned stimulus compared to controls. Given the devastating effects of drug addiction, identification of a potential pharmacological intervention in the reduction of relapse would be of great value. Therefore, future research is needed to validate the use of PT150 in reducing behaviors associated with drug addiction. (PsycINFO Database Record

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

“…Session events were maintained and collected with MedPC software (ENV013; MED Associates Inc., St. Albans, VT) and videotaped by ANY-MAZE video tracking software (San Diego Instruments, San Diego, CA) for sign and goal tracking behavior. All of the procedures were based on previous rodent and quail studies (e.g., Meyer et al, 2012; Rice et al, 2018).…”

“…Oral administration of PT150 (40 mg/kg) has been shown to reduce sign tracking behavior in quail (Rice, Eaton, Prendergast, & Akins, 2018). However, in that study, oral administration of PT150 was difficult to control with regard to ensuring that the birds consumed all of the drug.…”

“…The SC route of administration offers higher bioavailability compared with the oral route. Therefore, to better understand dose-dependent effects of PT150, three doses were administered (20,40, and 60 mg/kg) with the 40 mg/kg dose being the same dose that was administered orally in the previous study (Rice et al, 2018). Furthermore, to examine the effect of PT150 on CORT concentrations, blood was taken before the first and last day of conditioning and on the first and last day of PT150 administration.…”

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

“…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 ).…”

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

“…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.…”