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Updated: Mar 25, 2026
Protocol for Studying Extinction of Conditioned Fear in Naturally Cycling Female Rats
Published on: February 23, 2015
Serotonin depletion eliminates sex differences with respect to context-conditioned immobility in rat
Robert Pettersson1, Sven Melker Hagsäter1, Elias Eriksson2
1Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Box 431, SE-405 30, Gothenburg, Sweden.
Rationale:
Previous studies have shown that male rats display more anxiety-like behavior than females as assessed using the elevated plus maze and that serotonin depletion abolishes this difference by exerting an anxiolytic-like effect in males only.
Objectives:
To compare male and female rats with respect to immobility and startle responses to sudden noise bursts after contextual fear conditioning and to explore to what extent any possible sex difference in this regard is influenced by serotonin depletion during testing (but not acquisition).
Results:
In line with previous studies, males displayed more immobility following contextual conditioning induced by previous exposure to foot shocks than females. In males but not females, the immobility response was reduced by administration of the serotonin synthesis inhibitor para-chlorophenylalanine (PCPA) between shock exposure and testing, the consequence being that males and females no longer differed in this regard. Untreated males but not females displayed a negative correlation between fear-conditioned startle and immobility, suggesting that the latter behavior, when excessive, interferes with the former. In line with this assumption, the reduction in immobility following administration of PCPA in males coincided with an increase in startle that was not observed in females, hence revealing a sex difference in startle not seen in untreated controls.
Conclusion:
The greater display of context-conditioned immobility in males compared with females appears to be serotonin-dependent.
