differing ones for males versus females. Finally, 1 will discuss how these sexually dimorphic and diergic responses to life experience may be used to model sex despite differences in mental disorders, such as depression and posttraumatic stress disorder. Sex differences in learning and memory There are numerous reports of sex differences in basic learning processes.1,2 However, they vary greatly depending on the task used and species involved. In general, men tend to outperform women on tasks that require mental Inhibitors,research,lifescience,medical and spatial rotation, whereas women tend to outperform men when tested for spatial location in a static environment. Also, men are much

more accurate at aiming an object at a target, whereas women often excel at tasks that require fine motor skills. Some of these sex differences in Inhibitors,research,lifescience,medical performance, such as those for targeting, also exist in nonhuman primates.3 With respect, to the most common laboratory animal, the rat, sex differences in performance are influenced by natural differences in activity levels. Female rats, who are generally more active than male rats, perform best, on tasks that require

activity, such as active avoidance, and do quite poorly on those that require immobility, such as during fear conditioning Inhibitors,research,lifescience,medical or passive avoidance (for a review, see reference 4). Because sex differences in activity may confound differences in learning, we have adopted a task that Inhibitors,research,lifescience,medical does not depend on voluntary activity: classical conditioning of the eyeblink response. During this task, the animal is exposed to an aversive stimulation of the eyelid, which

causes it to blink. During training, the stimulation is preceded by a tone, which predicts the onset, of the stimulation. After repeated exposure to these paired stimuli, the animal “learns” that the tone predicts the eyelid stimulation and blinks in response Inhibitors,research,lifescience,medical to it. This task has a number of advantages for studying sex differences in learning. First, the eyeblink is a discrete response that can be accurately measured and quantified. Second, performance of this task is not. dependent on overt activity or exploration. The animal must, emit an unconditioned response to the eyelid stimulation AV-951 and only upon training elicits a conditioned response to the tone. As an additional advantage, the anatomical substrates that underlie learning the basic response have been identified.5,6 Finally and perhaps most, importantly, the task can be and has been conducted in virtually all animals, from mice to rats to monkeys to humans.7,8 Since results from animal studies often generate novel hypotheses about human behavior, this paradigm affords the possibility of testing them directly in normal and patient, populations. Using this task of classical eyeblink conditioning, we have observed that female rats acquire the learned response faster and emit more learned responses during training than do males.