Vogel conflict test: sex differences and pharmacological validation of the model

Anxiety disorders affect approximately 20% of the population, and women are twice as likely as men to develop anxiety disorders. Despite these findings, little is known about the effects of gender on tolerability and therapeutic efficacy of anxiolytic drugs. Sex differences are also observed in rodents, even though the majority of preclinical behavioral studies are conducted on males. The aim of this study was to investigate sex differences in anxiety-like behavior using the Vogel conflict test and the pharmacological responsiveness to a variety of psychoactive drugs in rats. Pharmacological treatments clinically used for the treatment of anxiety were tested in male and female rats. Overall, female rats accepted fewer punished responses, had lower levels of water intake even when matched for weight, and had a lower pain threshold for electrical footshock than males. Diazepam and chlordiazepoxide displayed anxiolytic-like effects in both genders. In contrast, buspirone, propranolol, fluoxetine and paroxetine showed activity only in male rats. Morphine had no anxiolytic-like activity in either gender. Analysis of the estrous cycle did not reveal any effect of cycle stage on behavioral or drug responses. This investigation highlights the importance of using female subjects in the preclinical research of anxiety and the screening of anxiolytic compounds in the drug development process.