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Updated: Feb 3, 2026

Protocol for Studying Extinction of Conditioned Fear in Naturally Cycling Female Rats
Published on: February 23, 2015
Extinction to amphetamine-associated context in female rats is dependent upon conditioned orienting
E N Hilz1, S M Lewis2, S Park3
1Department of Psychology, The University of Texas at Austin, 108 E. Dean Keeton Stop A8000, Austin, TX, 78712-1043, USA.
Rationale:
Females are considered more susceptible to the reinforcing effects of drugs and subsequently at increased risk for drug abuse and relapse after treatment. Estrogen is known to facilitate drug effects in females. However, other factors which contribute to the incidence of drug abuse are important to identify in order to recognize early risk factors and develop effective prevention and treatment schemes. Cue-directed behavior (aka sign tracking) has been implicated as a behavioral phenotype which identifies populations susceptible to drug abuse, partly due to its association with impulsivity and heightened dopamine function.
Objectives And Methods:
In this study, we investigate the viability of conditioned orienting (a form of cue-directed behavior) as a potential phenotype which predicts drug proclivity in female rats. In addition, we examine any influence endogenous female hormones across the estrous cycle may have on conditioned orienting and drug proclivity.
Results And Conclusions:
Utilizing an amphetamine-conditioned place preference task, results suggest that the orienting phenotype is an effective predictor of drug proclivity in females. Rats exhibiting enhanced orienting behavior show more robust preference for an amphetamine-associated context and are more resistant to extinction of this preference than nonorienting counterparts. Furthermore, both conditioned orienting behavior and conditioned place preference are minimally influenced by the estrous cycle.
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