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.     

Differential effects of cholinergic blockade on performance of rats in the water tank navigation task and in a radial water maze.

Tested the disruptive effect of cholinergic blockade under conditions in which either the working memory or the spatial mapping requirements of the behavioral task were emphasized. In Exp I, 13 male hooded rats were trained in an 8-arm radial water maze to asymptotic performance. When delays of 5, 10, 20, and 40 min were inserted between Choice 4 and Choice 5, incidence of errors in Choices 5–8 increased after pretrial (20 min) intraperitoneal scopolamine (0.2 mg/kg) faster than under control conditions and approached chance level with the 40-min delay. Scopolamine after Choice 4 or pretrial methylscopolamine was ineffective. In Exp II, 30 Ss were trained in a Morris water tank. Acquisition was impaired by pretrial injection (20 min) of 0.1 and 0.2 mg/kg scopolamine, but a higher dose (1.0 mg/kg) was required to impair overtrained performance. In a working memory version of the navigation task, scopolamine administered 20 min before the 1st trial deteriorated retention tested 40 min later at a dose of 1.0 but not at 0.4 and 0.2 mg/kg. It is concluded that the disruptive effect of scopolamine is proportional to the demands on the working memory component of the task, whereas the use of an overtrained mapping strategy is relatively resistant to cholinergic blockade. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex-related differences in cortical function after medial frontal lesions in rats.

The effects of sex on the performance of 4 spatial mazes (Morris water task, landmark task, radial arm maze, and egocentric radial arm maze) were studied in male and female rats given medial frontal lesions. Operated rats from both sexes were impaired at all of the tasks, but the frontal males were much less impaired than frontal females on the Morris task and the radial arm maze, both of which require animals to use multiple visual-spatial cues for their successful solution. Males also performed better on the egocentric maze. In contrast, frontal females performed better than frontal males at the landmark task, which is best solved by using a single spatial cue. The only sex difference in unoperated rats was a small advantage for females on the egocentric task. The sex differences may reflect an underlying difference in cortical organization or a differential response to cortical lesion in males and females. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Performance of male and female children, adolescents and adults on spatial tasks that involve everyday objects and settings.

Administered 9 spatial tasks to 52 male and 52 female children (aged 7–9 yrs), 30 male and 33 female adolescents (aged 18–19 yrs), and 46 male and 48 female undergraduate (adult) Ss. Eight of the tests involved stimuli and settings with which Ss would have everyday experience. Significant sex differences were observed on 2 of the 9 tasks: estimating the length of a floor and identifying embedded figures. Adults performed better than other age groups on the embedded figures task and a wall height estimation task. In those cases where sex differences were observed, the effect sizes were well below .100, suggesting the magnitudes of sex differences were minimal. The fact that no sex differences were found on 7 or the 9 spatial tasks allows, at most, the statement that males perform better than females on some spatial tasks. There is no justification for the global statement that males excel in spatial abilities. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Social play soliciting by male and female juvenile rats: Effects of neonatal androgenization and sex of cagemates.

Investigated the behavior of male and female Long-Evans hooded rats during individual exposure to nonplayful juvenile social stimuli in a novel test of play-soliciting behavior in 2 experiments examining hormonal and experiential determinants of sex differences. In Exp I, using 36 female and 18 male Ss, neonatally androgenized females engaged in play soliciting at a level equal to that of male controls and greater than that of nonandrogenized female controls. In Exp II, 52 males and 32 females were reared in unisexual and bisexual groups in order to compare long-term sex-related social experience effects on juvenile play soliciting. Males exposed only to other young males engaged in greater play soliciting than males exposed to both sexes; females, in contrast, were unaffected by sex of cagemates. Within rearing conditions, however, males engaged in greater play soliciting than females. The combined results suggest that perinatal gonadal androgen exposure effects on social play are prepotent and contribute essentially to sex differences in the initiation of social play behavior. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex, Age, and Training Modulate Spatial Memory in the Rhesus Monkey (Macaca mulatta).

The authors tested 90 rhesus monkeys (Macaca mulatta) on a task of spatial memory, the spatial Delayed Recognition Span Test. The results showed that performance declined significantly with age, males had greater scores than females, and the rate of apparent decline with age was greater in males than in females. Both working and reference memory declined with age, but only working memory showed sex differences. The authors compared these data with that of 22 monkeys who were trained on a simpler version of the task before formal testing. Training had no effect on males but dramatically improved working memory in young females. The results confirm a male advantage in spatial working memory at a young age and confirm a greater decline with age in males than in females. It is important to note that prior training completely reverses the deficits of young females. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The motive to avoid success and its effect on performance in school-age males and females.

169 male and 168 female 5th-11th graders completed a TAT-like measure of motive to avoid success in a developmental replication of M. S. Horner's (1968) study of the motive to avoid success. Ss also performed a series of tasks in competitive and noncompetitive conditions. No sex differences or clear age trends in motive-to-avoid-success imagery were found; however, there were sex and grade differences in the reasons given for avoiding success. In general, Ss, regardless of motive-to-avoid-success status, performed better in noncompetitive than competitive conditions. Developmental data show a tendency for 9th- and 11th-grade females with motive to avoid success to perform better in noncompetitive conditions, while older females without motive to avoid success perform better in competitive conditions. Males in the 8th, 9th and 11th grades with motive to avoid success performed better in a competitive condition, while their peers without motive to avoid success performed better in a noncompetitive condition. Results question that the motive to avoid success is aroused in the same experimental situations, that is, affects performance similarly, for males and young females as for older females. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex Differences in Visuo-Spatial Ability: Task Difficulty, Speed-Accuracy Tradeoff, and Other Performance Factors.

Males have consistently been found to perform better than females on a task that requires the subject to mentally rotate a figure. Recently, Goldstein, Haldane, and Mitchell (1990) suggested that performance factors are operative in explaining sex differences in spatial ability. However, Stumpf (1993) was unable to replicate all of Goldstein et al.'s (1990) findings and to generalize them to other measures of spatial ability. In this study, it was hypothesized (1) that females would take longer to respond and would get fewer correct items than males on a spatial rotation task, and (2) that only females would show a speed-accuracy tradeoff as the difficulty of the spatial task increased from the 90° to 180° rotated conditions. The results confirmed each of these hypotheses. Furthermore, as Stumpf (1993) found, when ratio scores from the number of items correct to number attempted were computed for both males and females, differences in spatial ability were reduced, though still evident. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interactions between 192-IgG saporin and intraseptal cholinergic and GABAergic drugs: Role of cholinergic medial septal neurons in spatial working memory.

Rats were administered 192-IgG saporin (SAP) or vehicle into the medial septum-vertical limb of the diagonal band (MS-vDB). Starting 1 week later, the effects of intraseptal scopolamine, oxotremorine, and muscimol were tested in a T-maze alternation task. Choice accuracy in the absence of infusions did not differ between control and SAP-treated rats. Intraseptal scopolamine or muscimol impaired the choice accuracy of SAP-treated but not control rats. Oxotremorine impaired accuracy similarly in control and SAP-treated rats. The enhanced effects of scopolamine and muscimol produced by SAP are consistent with the hypothesis that cholinergic MS-vDB neurons are used in spatial working memory. The finding that SAP alone did not alter choice accuracy provides further evidence that cholinergic MS-vDB neurons are not necessary for spatial working memory. Thus, cholinergic MS-vDB neurons are involved in but not necessary for spatial working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Testosterone potentiates scopolamine-induced disruptions of nonspatial learning in gonadectomized male rats.

Whereas research into the effects of the gonadal hormones on learning and memory has primarily focused on estrogen in females, recent evidence suggests that testosterone can also modulate learning in males through an interaction with the cholinergic system. In the present study, the interactive effects of testosterone and scopolamine (0.1- 0.32 mg/kg), a muscarinic receptor antagonist, on complex behavioral processes were investigated in male rats trained to respond under a multiple schedule of repeated acquisition and performance. In the acquisition component, subjects acquired a different 3-response sequence each session, whereas in the performance component, they responded on the same 3-response sequence each session. Although gonadectomy did not disrupt responding in either component, gonadectomized rats were less sensitive to the disruptive effects of scopolamine on both response rate and accuracy. In contrast, after receiving exogenous testosterone replacement, these gonadectomized males were more sensitive to the behavioral disruptions produced by scopolamine (i.e., the effects of scopolamine were similar to those obtained in gonadally intact males). These results suggest that testosterone replacement can enhance scopolamine-induced behavioral effects in gonadectomized male rats responding under a multiple schedule of repeated acquisition and performance, a finding that is in contrast to those previously found for certain spatial tasks. Furthermore, the present findings suggest that testosterone may decrease the activity of the cholinergic system during nonspatial tasks and thereby work in concert with the antagonism produced by scopolamine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in performance in the Morris water maze and the effects of initial nonstationary hidden platform training.

Sex differences in rats' performance on a stationary hidden-platform task (spatial task) in the Morris water maze and the effects of initial nonstationary hidden platform training (NSP training) were examined. The NSP training was designed to familiarize rats with the general requirements of the water-maze task without providing spatial information. NSP training led to faster acquisition and improved retention of the subsequent spatial task in both males and females. There was a sex difference favoring males on acquisition and retention of the spatial task only in rats that had not received previous NSP training. Moreover, there was an apparent reversed sex difference favoring females on some measures of spatial performance in NSP-trained rats. These results suggest that performance on the water-maze task, including the expression of sex differences, can be altered by previous familiarization with nonspatial aspects of the task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intestinal hypertrophy after small intestinal bypass in the rat. Studies on methods and reversibility of changes

This study assessed sex differences in spontaneous wheel running and maze performance in relation to puberal status in rats. No sex differences were found prepuberally in either task whereas, postpuberally, females exceeded males in wheel running and males made fewer maze errors than females. Postpuberal males and females were less active than independent groups of prepuberal males and females, respectively. Although mature females made more errors than prepuberal females, no differences were found between independent groups of pre- and postpuberal males.     

How habitat features shape ground squirrel (urocitellus beldingi) navigation.

The purpose of this investigation was to determine whether Belding's ground squirrels (Urocitellus beldingi) from areas rich in beacons perform differently in a task of spatial memory compared with squirrels from beacon-thin areas. To assess the role of environmental experience in spatial memory, wild-born squirrels with several days of experience in the field were compared with squirrels born in a lab and with no experience in their original habitat. Over two summers, squirrels captured from beacon-dense and beacon-thin areas were tested in a radial maze interspersed with beacons, using number of trials to criterion as a measure of spatial memory. To evaluate the effect of landmark navigation, in year 2 juveniles were prevented from seeing outside the maze area. In both years squirrels from beacon-dense populations reached criterion faster than squirrels from beacon-thin populations, and a weak rearing effect was present in 1 year. Despite sex differences in adult spatial skills, no differences were found between males and females in the maze. This demonstrates variation in the navigation strategies of young U. beldingi, and highlights the need to evaluate spatial preferences as a function of population or ecology in addition to species and sex. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sexual differentiation of play behavior in the ferret.

Three experiments examined the endocrine mechanisms responsible for sex differences in prepubertal play behavior of ferrets. In Exp I, 6 gonadally intact adolescent males exhibited higher levels of "stand-over" behavior than 6 females did in tests between 63 and 123 days of age with gonadally intact female partners of the same age. In Exp II, with 69 Ss, those Ss exposed to androgen or to ovarian steroids over Days 5–20 of postnatal life subsequently exhibited significantly higher levels of stand-over behavior in tests with females than did control females gonadectomized on Day 5 and not given steroids. None of the Ss in Exp II exhibited levels of stand-over behavior comparable to those of the gonadally intact males in Exp I. In Exp III, with 36 Ss, males gonadectomized and implanted subcutaneously with testosterone capsules on Day 70 and tested with females at 84–96 days of age exhibited levels of stand-over behavior comparable to those observed in Exp I in gonadally intact males of the same age (Weeks 12–24). Males gonadectomized on Day 70 and given no hormone at testing exhibited significantly lower levels of this behavior. Significantly lower levels were also exhibited by males gonadectomized on Day 35 and females gonadectomized on Day 70, regardless of whether they were tested with testosterone present after Day 70. Sex differences in the expression of prepubertal play behavior of ferrets apparently result from differential exposure of males and females to androgen over an extended postnatal period. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

DNA-protein interactions in the proximal zeta-globin promoter: identification of novel CCACCC- and CCAAT-binding proteins

The present study assessed whether prenatal androgen and estrogen exposure affected adult spatial learning and hippocampal morphology. Water maze performance, the CA1 and CA3 pyramidal cell field, and the dentate gyrus-granule cell layer (DG-GCL) morphology were assessed at adulthood (70+ days of age) in males, females, androgen-treated (testosterone propionate, TP, or dihydrotestosterone propionate, DHTP) females (2-4 mg/day), estradiol benzoate (EB)-treated females (100 microgram/day), and males treated with the antiandrogen flutamide (8 mg/day). Pregnant rats were injected daily (sc) between Embryonic Day 16 and birth; all pups were delivered by cesarean section. Flutamide-treated males were castrated upon delivery, and adult castrates were used to control for activational effects. Steroid-sensitive sex differences were observed in water maze performance in favor of males. Males had larger CA1 and CA3 pyramidal cell field volumes and soma sizes than females, which were feminized with flutamide treatment. TP and EB, but not DHTP, masculinized CA1 pyramidal cell field volume and neuronal soma size; CA3 was masculinized in both TP- and DHTP-treated females, while EB was ineffective. No effects were observed in cell density, number, or DG-GCL volume or due to adult hormone levels. Thus, prenatal androgens and estrogen influence sex differences in adult spatial navigation and exert differential effects on CA1 and CA3 pyramidal cell morphology. Hence, in addition to the previously reported postnatal component, there is also a prenatal component to the critical period in which gonadal steroids organize the neural mechanisms underlying sex differences in adult spatial ability.     

Sexual variation in behaviour during spatial and verbal tasks.

Detailed observations of behavior were obtained from 12 male and 12 female right-handed college students while they performed spatial or verbal tasks. Females emitted more rotational hand movements than males during a mental rotation task, and more vocalizations during an oral fluency task. Nonrotational behaviors, verbalizations, accuracy, and error scores did not vary according to task or sex, but females took significantly longer to complete the spatial task. Findings raise questions about the role of task-related movement patterns in spatial problem solving. (French abstract) (10 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alcohol intake in selected lines of mice: Importance of sex and genotype.

Studied the relationship between CNS sensitivity to ethanol (E) and voluntary consumption of an E solution in mice selected by G. E. McClearn and R. Kakihana (1973) for differences in E-induced sleep time. In Exp I, 32 mice from the long-sleep (LS) and short-sleep (SS) lines were offered a choice of water or solution GS consisting of 3% glucose and .16% sodium saccharin (w/v); or a choice of water or solution GS?+?E that contained GS solution plus 4% E (w/v). In Exp II, Ss from the 1st experiment were provided with a 3-way choice among water, solution GS, and solution GS?+?E. In both experiments, SS (alcohol-insensitive) Ss consumed more GS?+?E than LS (alcohol-sensitive). In addition, females drank considerably more GS?+?E solution than males. Thus consumption of sweetened E in both a 2-way choice (water and GS?+?E) and a 3-way choice (water, GS, and GS?+?E) was dependent on both genotype and sex. High genetic sensitivity to E was associated with low consumption, and vice versa. Although females consumed more alcohol than males, females of these lines have not been previously found to show lower sensitivity to acute alcohol administration. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Runway alternation and discrimination of mice with limbic lesions.

Trained 7 normal male HS mice (Norm), and 18 mice with septal (Sept) and cingulate-anterior limbic cortex lesions (Cing) in a straight-alley single-alternation task. Sept Ss performed significantly better than Norms, running faster on reinforced trials and slower on nonreinforced trials. Cing Ss performed as well as Norms. In a 2nd experiment with 64 Ss, Norm and Sept Ss learned a discrimination task using a food pellet or sound of a buzzer as a cue for either reinforced or nonreinforced trials. Sept Ss learned the food-cued task faster than Norms when nonreinforced trials were cued; Norms performed better when reinforced trials were cued with the buzzer. Results suggest that septal lesions enhance the cue value of food, and contradict the hypothesis that the septum is involved in response inhibition. (19 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Validity and fairness of physical ability tests for predicting performance in craft jobs.

Problems relating to performance, accidents, and turnover in outdoor telephone craft jobs stimulated 2 experiments aimed at developing and validating a physical test battery. Based on job analysis results, a battery of 9 measures was administered to a sample of 128 Ss (83 males and 45 females) in Exp I. A 2-test battery (dynamic arm strength and reaction time), valid for predicting job task performance and turnover, was selected. Regression equations for males and females were not significantly different. Exp II included a sample of 210 Ss (132 males and 78 females). A 3-test battery consisting of a body density measure, a balance test, and a static strength test was selected based on relationships with training performance. No significant differences were found in the regression equations for males compared to females. The Exp II battery was also significantly related to field performance, training completion, and accidents and was valid for the Exp I criteria. (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of muscarinic cholinergic receptor blockade in the rat anterior cingulate and Prelimbic/Infralimbic cortices on spatial working memory

Previous findings indicate that cholinergic input to the medial prefrontal cortex may modulate mnemonic processes. The present experiment determined whether blockade of muscarinic cholinergic receptors in the rodent anterior cingulate and prelimbic/infralimbic cortices impairs spatial working memory. In a 12-arm radial maze, a working memory for spatial locations task was employed using a continuous recognition go/no-go procedure. Rats were allowed to enter 12 arms for a reinforcement. Of the 12 arm presentations, 3 or 4 arms were presented for a second time in a session that did not contain a reinforcement. The number of trials between the first and second presentations of an arm ranged from 0 to 6 (lags). Infusions of scopolamine (1, 5, and 10 microgram), a muscarinic cholinergic antagonist, into the prelimbic/infralimbic cortices, but not the anterior cingulate cortex, significantly impaired spatial working memory in a lag- and dose-dependent manner. The deficit induced by scopolamine (10 microgram) was attenuated by concomitant intraprelimbic/infralimbic injections of oxotremorine (2 microgram) a muscarinic cholinergic agonist. A separate group of rats was tested on a successive spatial discrimination task. Injections of scopolamine (1, 5, and 10 microgram) into the prelimbic/infralimbic cortices did not impair performance on the spatial discrimination task. These findings suggest that muscarinic transmission in the prelimbic/infralimbic cortices, but not the anterior cingulate cortex, is important for spatial working memory.