Sex differences in baseline and drug-induced behavioural responses in classical behavioural tests

Behavioural pharmacology relies on animal models which are primarily validated using the male laboratory rat. Many researchers solely employ male animals in studies; this is primarily due to concerns about the impact of variations in the female estrous cycle on behavioural responses. The objective of the present study therefore was to examine whether sex has any effect in some commonly employed behavioural pharmacology tests. Male and female Sprague Dawley rats were examined in the following behavioural pharmacology tests: diazepam (DZP) effects on anxiolytic behaviour in the elevated plus maze (EPM); desipramine (DMI) effects on immobility time in the forced swim test (FST); amphetamine (AMP) and apomorphine (APO) effects on locomotor activity in the homecage monitoring apparatus (HCMA). Baseline investigations revealed that females were more active than males in all three tests. DZP increased open arm time and entries for males but not for females. Similarly, significant reduction in immobility time with DMI was found for males in the FST, with no effect observed in females. There was a significant effect of AMP dose on distance moved for both sexes; the peak locomotor stimulating effects were seen following 1–2 mg kg− 1 AMP doses for males, while 0.5 mg kg− 1 produced the greatest effect in females. APO impaired locomotor activity in both sexes. These results demonstrate that male and female rats respond differently to psychotropic drugs. The absence of female responses to the effects of DZP and DMI in the EPM and FST respectively was due to the high baseline activity levels seen with females; thus behavioural tests must be designed to account for sex differences in baseline behaviours to allow for unambiguous extrapolation of the results.

► Female rats displayed greater activity in the OFT and reduced immobility in the FST.
► Females had greater percent open arm entries in the EPM than males.
► Females showed blunted sensitivity to anxiolytic and antidepressant drug effects.
► Amphetamine effects on locomotor activity were greater for females than males.