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

Abstract

A devastating feature of drug dependence is the susceptibility of relapse (40-60%) after stretches of abstinence. In both animal and human research, it has been demonstrated that cues (e.g., levers, paraphernalia) associated with drug reward can instigate renewed drug taking. Research has shown animals that attend to a cue that predicts reward more than the location of reward delivery when the cue is present (sign trackers) have an increase in corticosterone (CORT), a primary stress hormone when compared with animals that do not sign track. This interaction of sign tracking and CORT implicate CORT's effects as a possible pharmacological target for cue-induced relapse behaviors. PT150 is a novel glucocorticoid receptor antagonist that reduces the effects of CORT. Previous research has shown that oral administration of 40 mg/kg PT150 reduced sign tracking. To better understand dose-dependent effects and to control for more accurate doses, the current experiment hypothesized that PT150 (20/40/60 mg/kg) given by subcutaneous (SC) injection to male quail would reduce sign tracking to a keylight conditional stimulus that predicts a grain unconditioned stimulus dose dependently. Results showed that SC injection of 20 mg/kg PT150 reduced sign tracking, but 40 or 60 mg/kg did not. The main findings from the current study are that the glucocorticoid receptor antagonist PT150 reduces sign tracking behavior dose dependently, and SC administration may provide better bioavailability compared with our previous study that used an oral route of administration. The current findings support previous literature by suggesting that the glucocorticoid receptor may be a potential pharmacological target for reducing relapse-like behaviors. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Figure 1.

A. Mean response bias across days 1,5,6 and 10 for placebo, and treatment groups. * Significant difference between day 1 and 5, 5 and 6, and 6 and 10. + Significant difference between 20 mg/kg treatment group and all other groups on day 10. STing = sign tracking response bias score, GTing = goal tracking response bias score. Figure 1.B and C. Mean time spent sign tracking (B) and goal tracking (C) across days 1,5,6 and 10 for placebo and, treatment groups.* Significant difference between day 1 and 5. + Significant difference between 20 mg/kg treatment group and all other groups, on day 10.

Figure 2.

Correlations between the response bias and plasma corticosterone (CORT) concentrations (ng/ml), on day 10 for each treatment group. # trending positive correlation between 20 mg/kg treatment group and the response bias on day 1, p = 0.05. GTing = goal tracking response bias, STing = sign tracking response bias.