Robust Sex Differences Research Articles

Who Cares About Marrying a Rich Man? Intelligence and Variation in Women’s Mate Preferences

Although robust sex differences are abundant in men and women’s mating psychology, there is a considerable degree of overlap between the two as well. In an effort to understand where and when this overlap exists, the current study provides an exploration of within-sex variation in women’s mate preferences. We hypothesized that women’s intelligence, given an environment where women can use that intelligence to attain educational and career opportunities, would be: (1) positively related to their willingness to engage in short-term sexual relationships, (2) negatively related to their desire for qualities in a partner that indicated wealth and status, and (3) negatively related to their endorsement of traditional gender roles in romantic relationships. These predictions were supported. Results suggest that intelligence may be one important individual difference influencing women’s mate preferences.

The kisspeptin system of the human hypothalamus: sexual dimorphism and relationship with gonadotropin‐releasing hormone and neurokinin B neurons

Kisspeptin signaling via the kisspeptin receptor G-protein-coupled receptor-54 plays a fundamental role in the onset of puberty and the regulation of mammalian reproduction. In this immunocytochemical study we addressed the (i) topography, (ii) sexual dimorphism, (iii) relationship to gonadotropin-releasing hormone (GnRH) neurons and (iv) neurokinin B content of kisspeptin-immunoreactive hypothalamic neurons in human autopsy samples. In females, kisspeptin-immunoreactive axons formed a dense periventricular plexus and profusely innervated capillary vessels in the infundibular stalk. Most immunolabeled somata occurred in the infundibular nucleus. Many cells were also embedded in the periventricular fiber plexus. Rostrally, they formed a prominent periventricular cell mass (magnocellular paraventricular nucleus). Robust sex differences were noticed in that fibers and somata were significantly less numerous in male individuals. In dual-immunolabeled specimens, fine kisspeptin-immunoreactive axon varicosities formed axo-somatic, axo-dendritic and axo-axonal contacts with GnRH neurons. Dual-immunofluorescent studies established that 77% of kisspeptin-immunoreactive cells in the infundibular nucleus synthesize the tachykinin peptide neurokinin B, which is known to play crucial role in human fertility; 56 and 17% of kisspeptin fibers in the infundibular and periventricular nuclei, respectively, contained neurokinin B immunoreactivity. Site-specific co-localization patterns implied that kisspeptin neurons in the infundibular nucleus and elsewhere contributed differentially to these plexuses. This study describes the distribution and robust sexual dimorphism of kisspeptin-immunoreactive elements in human hypothalami, reveals neuronal contacts between kisspeptin-immunoreactive fibers and GnRH cells, and demonstrates co-synthesis of kisspeptins and neurokinin B in the infundibular nucleus. The neuroanatomical information will contribute to our understanding of central mechanisms whereby kisspeptins regulate human fertility.

Why Sex Matters: Brain Size Independent Differences in Gray Matter Distributions between Men and Women

The different brain anatomy of men and women is both a classic and continuing topic of major interest. Among the most replicated and robust sex differences are larger overall brain dimensions in men, and relative increases of global and regional gray matter (GM) in women. However, the question remains whether sex-typical differences in brain size (i.e., larger male and smaller female brains) or biological sex itself account for the observed sex effects on tissue amount and distribution. Exploring cerebral structures in men and women with similar brain size may clarify the true contribution of biological sex. We thus examined a sample of 24 male and 24 female subjects with brains identical in size, in addition to 24 male and 24 female subjects with considerable brain size differences. Using this large set of brains (n = 96), we applied a well validated and automated voxel-based approach to examine regional volumes of GM. While we revealed significant main effects of sex, there were no significant effects of brain size (and no significant interactions between sex and brain size). When conducting post hoc tests, we revealed a number of regions where women had larger GM volumes than men. Importantly, these sex effects remained evident when comparing men and women with the same brain size. Altogether, our findings suggest that the observed increased regional GM volumes in female brains constitute sex-dependent redistributions of tissue volume, rather than individual adjustments attributable to brain size.

Characterization of spatial performance in male and female Long-Evans rats by means of the Morris water task and the ziggurat task

Sex differences are prominent influences on spatial performance. One of the most common tasks to assess sex differences in spatial navigation in rodents is the Morris water task (MWT). In this task rats swim in a pool of water to locate a hidden platform employing the topographical relationships among the distal visual cues, pool wall, and goal location. Some evidence suggests that male rats display superior performance relative to females in the MWT. It is unknown, however, to what extent the sex difference in rats is task-dependent. This study compared the performance of male and female Long-Evans rats in the wet-land MWT versus the dry-land ziggurat task (ZT). The ZT represents a new dry-land task in which rats explore an arena with 16 ziggurat pyramids to locate food rewards. Several behavioural parameters, including latency, path length, path speed, probe trial performance, errors, and the number of returns were used as indices of spatial learning and memory. While males and females did not display significant differences in the traditional measures of spatial navigation within MWT, they displayed a robust sex difference in all measures of the ZT. These results indicate task-specific sex differences in spatial performance. Our findings suggest that males and females may employ different learning strategies in the MWT and ZT and that the latter task provides a more favourable task for assessing sex differences in rats.

Differential responsiveness in brain and behavior to sexually dimorphic long calls in male and female zebra finches

In zebra finches (Taeniopygia guttata), as in most other songbird species, there are robust sex differences in brain morphology and vocal behavior. First, male zebra finches have larger song system nuclei--involved in sensorimotor learning and production of song--than females. Second, male zebra finches learn their song from a tutor, whereas female zebra finches develop a learned preference for the song of their father but do not sing themselves. Third, female zebra finches produce an unlearned "long call," while males learn their long call (which is different from that of females) from their song tutor. We investigated behavioral and molecular neuronal responsiveness to this sexually dimorphic communication signal. Behavioral responsiveness was quantified by measuring the number of calls and approaches in response to calls that were broadcast from a speaker. We quantified neuronal activation by measuring the number of neurons expressing Zenk, the protein product of the immediate early gene ZENK, in a number of different forebrain regions in response to male calls, to female calls, or to silence. In both sexes female calls evoked more calls and approaches than male calls. There was significantly greater Zenk expression in response to female calls compared to silence in the caudomedial nidopallium, caudomedial mesopallium, and the hippocampus in females, but not in males. Thus, male and female zebra finches both show a behavioral preference for female calls, but differential neuronal activation in response to sexually dimorphic calls.

Sex-specific response strategies in mental rotation

The present study investigated whether the marked sex difference in the original mental rotation test (MRT) is simply a result of sex differences in response strategies. Thirty-four participants (17 males, 17 females) completed the revised Vandenberg and Kuse MRT [Peters, M., Laeng, B., Latham, K., Jackson, M., Zaiyouna, R., & Richardson, C. (1995). A redrawn Vandenberg & Kuse Mental Rotations Tests: Different versions and factors that affect performance. Brain and Cognition, 28, 39–58.] and a modified MRT. In the modified version, the number of matching figures varied from zero to four, so that participants had to match every single figure to the target, impeding leaps. Both men and women showed reduced performance in the modified version. However, men were clearly more affected than women. Although sex differences in the modified MRT were somewhat reduced, men still outperformed women (original MRT: d = .95, modified MRT: d = .76). The findings suggest that men rely more on a leaping response strategy than women, however, the robust sex differences in MRT was only marginally affected by sex differences in response strategies.

Virtual navigation in humans: the impact of age, sex, and hormones on place learning

Certain cognitive processes, including spatial ability, decline with normal aging. Spatial ability is also a cognitive domain with robust sex differences typically favoring males. However, tests of spatial ability do not seem to measure a homogeneous class of processes. For many, mentally matching rotated three-dimensional images is the gold standard for measuring spatial cognition in humans, while the Morris water task (MWT) is a preferred method in the domain of nonhuman animal research. The MWT is sensitive to hippocampal damage, a structure critical for normal learning and memory and often implicated in age-related cognitive decline. A computerized (virtual) version of the MWT (VMWT) appears to require and engage human hippocampal circuitry, and has proven useful in studying sex differences and testing spatial learning theories. In Experiment 1, we tested participants (20–90 years of age) in the VMWT and compared their performance to that on the Vandenberg Mental Rotation Test. We report an age-related deficit in performance on both tasks. In Experiment 2, we tested young (age 20–39) and elderly (age >60) participants in the VMWT and correlated their performance to the circulating levels of testosterone and cortisol. Our findings indicate that the persistence of male spatial advantage may be related to circulating testosterone, but not cortisol levels, and independent of generalized age-related cognitive decline.

Sex differences and repeated intravenous nicotine: behavioral sensitization and dopamine receptors

The present study examined the sex-dependent expression of behavioral sensitization as well as changes of dopamine (DA) transporters and D 1, D 2, and D 3 receptors following repeated intravenous nicotine administration. Male and female Sprague–Dawley rats were implanted with indwelling jugular catheters, equipped with subcutaneous intravenous injection ports. Rats were habituated to activity chambers for 3 days and were subsequently administered 15-s bolus injections of intravenous nicotine (50 μg/kg/ml) 1/day for 21 days. Animals were placed in activity chambers for 60 min immediately after the 1st and 21st nicotine injection. Observational time sampling was also performed. Brains were subsequently removed and frozen for autoradiographic DA transporter/DA receptor analysis on the afternoon females were in proestrus. With one exception, no robust sex differences were observed for locomotor activity or any rearing measures either during baseline or after initial nicotine injection. Females exhibited markedly more behavioral sensitization of locomotor activity, rearing, duration of rearing, and incidence of observed rearing. There were no sex differences in the number of D 1 or D 2 receptors. Females exhibited an increased number of DA transporters and decreased D 3 receptors in the NAcc, relative to males. Multiple regression analyses suggest that D 3 receptors and DA transporters in various striatal and NAcc subregions differentially predicted nicotine-induced behaviors for males and females. Collectively, these findings demonstrate that repeated intravenous nicotine produces sex differences in the expression of behavioral sensitization, and suggest that nicotine-induced changes of DA transporters and D 3 receptors are partly responsible for increased behavioral sensitization in female rats.

Dehydroepiandrosterone metabolism by 3beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase in adult zebra finch brain: sex difference and rapid effect of stress.

Dehydroepiandrosterone (DHEA) is a precursor to sex steroids such as androstenedione (AE), testosterone (T), and estrogens. DHEA has potent effects on brain and behavior, although the mechanisms remain unclear. One possible mechanism of action is that DHEA is converted within the brain to sex steroids. 3beta-Hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase (3beta-HSD) catalyzes the conversion of DHEA to AE. AE can then be converted to T and estrogen within the brain. We test the hypothesis that 3beta-HSD is expressed in the adult brain in a region- and sex-specific manner using the zebra finch (Taeniopygia guttata), a songbird with robust sex differences in song behavior and telencephalic song nuclei. In zebra finch brain, DHEA is converted by 3beta-HSD to AE and subsequently to estrogens and 5alpha- and 5beta-reduced androgens. 3beta-HSD activity is highest in the diencephalon and telencephalon. In animals killed within 2-3 min of disturbance, baseline 3beta-HSD activity in portions of the telencephalon is higher in females than males. Acute restraint stress (10 min) decreases 3beta-HSD activity in females but not in males, and in stressed animals, telencephalic 3beta-HSD activity is greater in males than in females. Thus, the baseline sex difference is rapidly reversed by stress. To our knowledge, this is the first demonstration of 1) brain region differences in DHEA metabolism by 3beta-HSD, 2) rapid modulation of 3beta-HSD activity, and 3) sex differences in brain 3beta-HSD and regulation by stress. Songbirds are good animal models for studying the regulation and functions of DHEA and neurosteroids in the nervous system.

Sex differences in prepulse inhibition deficits in chronic schizophrenia

Recent years have seen a dramatic growth in the number of studies using prepulse inhibition (PPI) paradigms to index information processing deficits in schizophrenia. There are, however, robust sex differences in PPI in healthy subjects, with women exhibiting less PPI than men in the absence of any psychopathology. To investigate the role of sex in prepulse modification deficits in the long-term course of schizophrenia, we assessed PPI (response inhibition with the prepulse preceding the pulse by 30–150 ms) and prepulse facilitation (PPF; response facilitation with the prepulse preceding the pulse by 1000 ms) of the acoustic startle response in 42 chronic schizophrenia patients (27 men; all 42 on typical antipsychotics) and 35 controls (15 men). The results revealed that healthy women showed less PPI than healthy men. Men with schizophrenia showed less PPI compared to healthy men, but women with schizophrenia did not differ in PPI from healthy women. Age of illness onset negatively correlated to PPI in male patients. There was no significant effect of sex in PPF, and although patients (regardless of sex) showed less PPF relative to controls, this effect was abolished when the current age was co-varied for. These findings indicate sex differences in PPI deficits in schizophrenia. Future studies of schizophrenia patients need to take sex and age of subjects into account to optimise the investigation of PPI deficits, and their clinical, neural, and pharmacological correlates.

Sex differences in interest in infants in juvenile rhesus monkeys: relationship to prenatal androgen

Yearling rhesus monkey females interact more with infants than do males. However, the continuity of this sex difference throughout the juvenile period is unknown. Human females display similar sexually differentiated interest in infants, and studies of girls with congenital adrenal hyperplasia suggest that this sex difference may be modulated by prenatal androgen exposure. We investigated infant interest in 1- to 3-year-old juvenile rhesus monkeys. Hormonal influences on this behavior were investigated by treating pregnant females with an androgen-receptor blocker (flutamide), testosterone enanthate, or vehicle, early or late in gestation. Subjects were reared in their well-established natal groups, composed of species-typical matrilineal social structures, including members of all ages. Yearling control females interacted with infants more than did yearling control males. At 2 and 3 years of age, the magnitude of the sex difference in interactions with infants increased markedly, producing effect sizes of more than 2.5 standard deviations. These effects are larger than those reported in humans. Androgen treatment did not affect male or female interactions with infants, but late gestation flutamide masculinized aspects of females’ interest in infants. Although early flutamide prevented complete masculinization of male genitalia, this treatment was not accompanied by any alterations in the masculine pattern of infant interest. We found no evidence that the robust juvenile sex difference in frequency of infant interactions results from socialization. However, it was largely unaffected by our hormone manipulations. Whether this reflects characteristics of our specific treatments or is evidence of nonhormonal influences on infant interest remains unanswered.

Photoperiod affects the expression of sex and species differences in leukocyte number and leukocyte trafficking in congeneric hamsters

Sex differences in immune function are well documented. These sex differences may be modulated by social and environmental factors. Individuals of polygynous species generally exhibit more pronounced sex differences in immune parameters than individuals of monogamous species, often displaying an energetic trade-off between enhanced immunity and high mating success. During winter, animals contend with environmental conditions (e.g. low temperatures and decreased food availability) that evoke energetic-stress responses; many mammals restrict reproduction in response to photoperiod as part of an annual winter coping strategy. To test the hypothesis that extant sex and species differences in immune surveillance may be modulated by photoperiod, we examined leukocyte numbers in males and females of two closely related hamster species ( Phodopus). As predicted, uniparental P. sungorus exhibited a robust sex difference, with total white blood cells, total lymphocytes, T cells, and B cells higher in females than males, during long days when reproduction occurs, but not during short days when reproduction usually stops. In contrast, biparental male and female P. campbelli exhibited comparable leukocyte numbers during both long and short days. To study sex differences in stress responses, we also examined immune cell trafficking in response to an acute (2 h) restraint stressor. During stressful challenges, it appears beneficial for immune cells to exit the blood and move to primary immune defense areas such as the skin, in preparation for potential injury or infection. Acute stress moved lymphocytes and monocytes out of the blood in all animals. Blood cortisol concentrations were increased in P. sungorus females compared to males at baseline (52%) and in response to restraint stress (38%), but only in long days. P. campbelli males and females exhibited comparable blood cortisol and stress responses during both long and short days. Our results suggest that interactions among social factors and the environment play a significant role in modulating sex and seasonal alterations in leukocyte numbers and stress responses.

Testosterone suppresses circadian responsiveness to social cues in the diurnal rodent Octodon degus.

The diurnal, social rodent Octodon degus displays a robust sex difference in the ability to use social cues to facilitate reentrainment following a phase advance of the light cycle. Adult females housed with a female social cue donor reentrained 25% to 40% faster than did females reentraining alone. However, reentrainment rates of males were unaffected by exposure to female social cues during reentrainment. The authors hypothesized that males were less sensitive to the reentrainment-enhancing effects of social cues and that their higher threshold to the stimuli could be overcome if the social cues were either increased in strength or salience. Housing a male with two females significantly shortened the time to reentrain following a 9-h phase advance (p = 0.002). Housing with a sister had no effect on reentrainment. Therefore, male degus are able to respond to social cues but require the stimulus to be stronger than that for females. The effect of testosterone was tested by comparing reentrainment rates of castrated males before and after testosterone replacement both with and without a female social cue donor. Castrated males responded to a single female social cue donor, reentraining 35% faster than when housed alone (p = 0.006), whereas the time to reentrainment of intact males and males with testosterone capsule implants did not differ. Intact females were also implanted with testosterone and phase shifted with and without donors. Testosterone treatment eliminated the increase in reentrainment rates in the presence of social cues. The authors conclude that the rate of recovery from odor-enhanced phase shifts is modulated by activational effects of testosterone in male degus. Testosterone is also effective in suppressing social cue responsiveness in females, suggesting that testosterone's effects on responsiveness are not sexually dimorphic. This hormonal effect likely occurs by altering sensory system functions or CNS response to sensory information.

EXPERIENTIAL FACTORS IN SEX DIFFERENCES ON MENTAL ROTATION

Past research has shown that men score significantly higher than women on mental rotation tests. The present study examined the effects of a prior exposure to a mental rotation task, i.e., adapted Cube Comparison test, and to three-dimensional objects, i.e., Legos™, on the performance on the Mental Rotation Test. 113 men and women were randomly divided into three conditions: control, exposure, or detailed instructions. On average, men outperformed women. Further analyses showed that sex differences were significant in the control condition but not in the other two, suggesting that a cuing effect may explain some of the robust sex differences in visuospatial tasks.

Estrogen receptor-alpha distribution in the human hypothalamus in relation to sex and endocrine status.

The present study reports the first systematic rostrocaudal distribution of estrogen receptor-alpha immunoreactivity (ERalpha-ir) in the human hypothalamus and its adjacent areas in young adults. Postmortem material taken from 10 subjects (five male and five female), between 20 and 39 years of age, was investigated. In addition, three age-matched subjects with abnormal levels of estrogens were studied: a castrated, estrogen-treated 50-year-old male-to-female transsexual (T1), a 31-year-old man with an estrogen-producing tumor (S2), and an ovariectomized 46-year-old woman (S8). A strong sex difference, with more nuclear ERalpha-ir in women, was observed rostrally in the diagonal band of Broca and caudally in the medial mamillary nucleus. Less robust sex differences were observed in other brain areas, with more intense nuclear ERalpha-ir in men, e.g., in the sexually dimorphic nucleus of the medial preoptic area, paraventricular nucleus, and lateral hypothalamic area, whereas women had more nuclear ERalpha-ir in the suprachiasmatic nucleus and ventromedial nucleus. No nuclear sex differences in ERalpha were found, e.g., in the central part of the bed nucleus of the stria terminalis. In addition to nuclear staining, ERalpha-ir appeared to be sex-dependently present in the cytoplasm of neurons and was observed in astrocytes, plexus choroideus, and other non-neuronal cells. ERalpha-ir in T1, S2, and S8 suggested that most of the observed sex differences in ERalpha-ir are "activational" (e.g., ventromedial nucleus/medial mamillary nucleus) rather than "organizational." Species similarities and differences in ERalpha-ir distribution and possible functional implications are discussed.

When I look into your eyes

Gender differences in communication styles have been observed in subjects of all ages, in many cultures. This study was designed to see whether such gender differences persist in happily married couples. Observers coded the nonverbal behaviors of 40 happily married US couples who were videotaped discussing commitment in marriage. Although these couples showed no significant sex differences in marital satisfaction (as measured by the MARQ of Russell and Wells) or in verbal statements regarding commitment, robust sex differences in the following nonverbal behaviors emerged: smiling, laughing, and average length of look at spouse (t-test for matched pairs, p <0.01). Wives looked significantly longer, as if listening attentively; husbands used shorter glances at wives, suggesting a monitoring function. Results were consistent across age and length of marriage. Experimenter effects were seen, in that husbands were more likely to speak first with a male experimenter, and discussions went on longer with a female...

The effects of uncertainty and sex in a crisis simulation game

We conducted an experimental test of spiraling behavior, sex differences, and uncertainty in a simulated crisis situation. We investigated the relationship between weapons acquisition and the likelihood of engaging in aggressive behavior, such as going to war. The sample included 100 male and female subjects who participated in a crisis simulation in same‐sex dyads; each student was instructed to role play the leader of a country in conflict with another leader over a nearby island replete with newly discovered oil resources. Participants were randomly assigned to stimulus materials that manipulated the certainty of the information they received about their partner's force structure. In four cycles of decision‐making, each participant made procurement decisions, took an action related to the conflict, including decisions about going to war, completed questionnaires on characteristics such as the hostility and trustworthiness of themselves and their opponents, and wrote messages to the other member of the pair. The results of the study demonstrate a strong relationship between weapons acquisition and hostility. In addition, we found large and robust sex differences, showing that men are much more likely than women to acquire weapons and engage in aggressive behavior at every stage. There was no effect of uncertainty on either arms procurement or aggression.

Sex Differences in Cocaine-Stimulated Motor Behavior: Disparate Effects of Gonadectomy

Sex differences in biological substrates of drug use and addiction are poorly understood. The present study investigated sexual dimorphisms in motor behavior following acute cocaine administration (10, 20, or 40 mg/kg, i.p.). Cocaine increased stereotypy rating, horizontal and vertical activity in both sexes, and effects were always greater in females than males. A population analysis using data from multiple experiments indicated that horizontal activity scores were normally distributed in males but not in females. Gonadectomy induced disparate effects on cocaine-stimulated motor behavior. Population analysis indicated that castrated males exhibited more horizontal activity and stereotypy than shams. Ovariectomy did not affect cocaine-stimulated stereotypy but did attenuate horizontal activity in a subset of rats that had not been vaginally lavaged. In summary, gonadectomy effects were sex and behavioral topography specific and indicate that activational effects of gonadal hormones partially mediate the robust sex differences in cocaine-stimulated open-field behavior.

Dopamine release and uptake are greater in female than male rat striatum as measured by fast cyclic voltammetry

The present studies investigated sexual dimorphisms in dopamine release and uptake using fast-scan cyclic voltammetry in anesthetized rats and in brain slices. Electrical stimulation of the medial forebrain bundle of anesthetized rats at high frequency (60 Hz) elicited significantly more extracellular dopamine in the caudate nucleus of females than males. This sex difference was apparent over a range of current intensities applied to the stimulating electrode. Local electrical stimulation of brain slices in vitro verified in vivo results as more extracellular dopamine was elicited by single and 10 pulse stimulations in the caudate nucleus of females. Kinetic analysis of in vivo and in vitro dopamine overflow data indicated that dopamine release (the concentration of dopamine released per stimulus pulse) and the maximal velocity of dopamine uptake are greater in female rats, but the affinity of the transporter for dopamine was the same in males and females. None of these three parameters varied across the female estrous cycle. Linear regression analysis of dopamine release versus maximal uptake velocity data indicated a significant association of release and uptake sites in each sex and regression lines for males and females virtually overlapped. One explanation for these results is greater dopamine neuron terminal density in female caudate nucleus. These sexual dimorphisms in dopaminergic neurotransmission provide a novel, plausible mechanism to explain robust sex differences in behavioral responses of rats to pyschostimulant drugs and may have implications for human neurological disorders and drug abuse.

Sexually dimorphic responses to neonatal basal forebrain lesions in mice: I. Behavior and neurochemistry.

The nucleus basalis magnocellularis (nBM) provides the primary source of cholinergic input to the cortex. Neonatal lesions of the nBM produce transient reductions in cholinergic markers, persistent abnormalities in cortical morphology, and spatial navigation impairments in adult mice. The present study examined sex differences in the effects of an electrolytic nBM lesion on postnatal day 1 (PND 1) in mice on behavior and neurochemistry in adulthood. Mice were lesioned on PND 1 and tested at 8 weeks of age on a battery of behavioral tests including passive avoidance, cued and spatial tasks in the Morris water maze, simple and delayed nonmatch to sample versions of an odor discrimination task, and locomotor activity measurements. Following behavioral testing, mice were sacrificed for either morphological assessment or neurochemical analysis of a cholinergic marker or catecholamines. There were no lesion or sex differences in acquisition or retention of passive avoidance, performance of the odor discrimination tasks, or activity levels. Control mice showed a robust sex difference in performance of the spatial water maze task. The lesion produced a slight cued but more dramatic spatial navigation deficit in the water maze which affected only the male mice. Neurochemical analyses revealed no lesion-induced changes in either choline acetyltransferase activity or levels of norepinephrine or serotonin at the time of testing. The subsequent report shows a sex difference in lesion-induced changes in cortical morphology which suggests that sexually dimorphic cholinergic influences on cortical development are responsible for the behavioral deficits seen in this study.