Gerianne M. Alexander

Sex differences in response to children's toys in nonhuman primates (Cercopithecus aethiops sabaeus)

Sex differences in children’s toy preferences are thought by many to arise from gender socialization. However, evidence from patients with endocrine disorders suggests that biological factors during early development (e.g., levels of androgens) are influential. In this study, we found that vervet monkeys (Cercopithecus aethiops sabaeus) show sex differences in toy preferences similar to those documented previously in children. The percent of contact time with toys typically preferred by boys (a car and a ball) was greater in male vervets (n=33) than in female vervets (n=30) (P<.05), whereas the percent of contact time with toys typically preferred by girls (a doll and a pot) was greater in female vervets than in male vervets (P<.01). In contrast, contact time with toys preferred equally by boys and girls (a picture book and a stuffed dog) was comparable in male and female vervets. The results suggest that sexually differentiated object preferences arose early in human evolution, prior to the emergence of a distinct hominid lineage. This implies that sexually dimorphic preferences for features (e.g., color, shape, movement) may have evolved from differential selection pressures based on the different behavioral roles of males and females, and that evolved object feature preferences may contribute to present day sexually dimorphic toy preferences in children. D 2002 Elsevier Science Inc. All rights reserved.

Midazolam: effects on amnesia and anxiety in children.

BACKGROUND The minimum time interval between administration of oral midazolam and separation of children from their parents that ensures good anterograde amnesia has not been previously determined. This is of particular importance in a busy operating room setting where schedule delays secondary to midazolam administration may not be tolerated. METHODS Children (n = 113) undergoing general anesthesia and surgery completed preoperative baseline memory testing using a validated series of picture cards and were randomly assigned to one of three midazolam groups or a control group. Exactly, 5, 10, or 20 min after receiving oral midazolam (0.5 mg/kg) or 15 min after receiving placebo, children were administered a second memory test that used pictures. Anxiety of children was assessed during induction of anesthesia with use of a validated anxiety measurement tool. Postoperatively, recall and recognition for picture cards seen during baseline testing and postintervention testing were assessed. RESULTS Postoperatively, recall and recognition of pictures presented to patients after drug administration (anterograde amnesia) showed significant group differences (P = 0.0001), with recall impaired in the 10- (P = 0.004) and 20-min groups (P = 0.0001). Similarly, recognition memory was impaired in the 5- (P = 0.0008), 10- (P = 0.0001) and 20-min (P = 0.0001) groups. Significant anxiolytic effects of midazolam were observed as early as 15 +/- 4 min after midazolam administration (P = 0.02). CONCLUSIONS Midazolam administered orally produces significant anterograde amnesia when given as early as 10 min before a surgical procedure.

Androgen–Behavior Correlations in Hypogonadal Men and Eugonadal Men☆☆☆

Mood and response to auditory sexual stimuli were assessed in 33 hypogonadal men receiving testosterone (T) replacement therapy, 10 eugonadal men receiving T in a male contraceptive clinical trial, and 19 eugonadal men not administered T. Prior to and after 6 weeks of hormone administration, men completed a mood questionnaire, rated sexual arousal to and sexual enjoyment of auditory sexual stimuli, and performed a dichotic listening task measuring selective attention for sexual stimuli. Mood questionnaire results suggest that T has positive effects on mood in hypogonadal men when hormone levels are well below the normal male range of values, but does not have any effects on mood when hormone levels are within or above the normal range. However, increased sexual arousal and sexual enjoyment were associated with T administration regardless of gonadal status. Eugonadal men administered T also increased in the bias to attend to sexual stimuli. In contrast, the comparison group of eugonadal men not administered T showed no mood or sexual behavior changes across the two test sessions. These data support a positive relationship between T and sexual interest, sexual arousal, and sexual enjoyment in men.

Posttraining intrahippocampal estradiol injections enhance spatial memory in male rats : Interaction with cholinergic systems

Male Long-Evans rats received an 8-trial training session in a spatial water maze task, followed by a unilateral posttraining intrahippocampal injection of either estradiol (1.0 microgram/0.5 microliter) or saline. Retention was tested 24 hr later, and latency to escape was used as a measure of memory. Retention test escape latencies of rats given intrahippocampal injections of estradiol were lower than those of saline-treated rats, indicating an enhancement of memory. Intrahippocampal injections of estradiol delayed 2 hr posttraining did not affect retention. In Experiment 2, the memory enhancing effect of intrahippocampal injection of estradiol was blocked by peripheral administration of a subeffective dose (0.1 mg/kg) of the cholinergic antagonist scopolamine. Intrahippocampal injections of estradiol enhance memory in male rats, and estradiol may influence memory through an interaction with muscarinic cholinergic systems.

Rewarding affective properties of intra-nucleus accumbens injections of testosterone

On alternating days, adult male Long-Evans rats implanted with bilateral cannulas in the nucleus accumbens received intracerebral injections of testosterone in a water-soluble cyclodextrin inclusion complex (0.125, 0.25, or 0.5 microg/0.5 microl saline) or saline immediately prior to being confined for 30 min to 1 of 2 compartments of a place-preference apparatus. All rats received 8 days of pairings (4 hormone and 4 saline). On Day 9 the rats were given a 20-min test session during which they had access to all compartments of the apparatus. No hormone was injected prior to the test session. On the test day, rats spent significantly more time in the compartment previously paired with bilateral intra-accumbens injections of testosterone (0.25 and 0.5 microg/0.5 microl saline) than in the compartment previously paired with saline injections. The findings indicate that intra-accumbens injections of testosterone are sufficient to produce reward.

Expression of Testosterone Conditioned Place Preference Is Blocked by Peripheral or Intra-accumbens Injection of α-Flupenthixol ☆

Previous evidence indicates that peripheral and intranucleus accumbens injections of testosterone have rewarding effects in male rats as measured in a conditioned place preference (CPP) paradigm. The present study investigated the neurochemical bases of the rewarding properties of testosterone by examining the effect of peripheral and intranucleus accumbens injection of the dopamine receptor antagonist alpha-flupenthixol on expression of testosterone-induced CPP. On alternating days, adult male Long-Evans rats received peripheral injections of testosterone in a water-soluble hydroxypropyl-beta-cyclodextrin (HBC) inclusion complex (0.8 mg/kg) or saline-HBC immediately prior to being confined for 30 min to one of two compartments of a place preference apparatus. All rats received 8 days of pairings (four hormone pairings, four saline pairings). On day 9 the rats were given a 20-min test session during which they had access to all compartments of the apparatus. No hormone was injected prior to the test session; however, rats received a peripheral (20 min prior; 0.2, 0.3 mg/kg) or intra-accumbens (2 min prior, 5.0 micrograms) injection of alpha-flupenthixol or saline. On the test day, rats receiving saline injections spent significantly more time in the compartment previously paired with injections of testosterone than in the compartment previously paired with vehicle injections. In contrast, rats receiving peripheral or intra-accumbens alpha-flupenthixol injections did not spend significantly more time in the compartment previously paired with testosterone. The blockade of testosterone CPP was not due to an effect of alpha-flupenthixol on motor behavior. The findings provide further evidence of the rewarding affective properties of testosterone and indicate that peripheral administration and intra-accumbens administration of alpha-flupenthixol block expression of testosterone CPP. The rewarding affective properties of testosterone are mediated, at least in part, via an interaction with the mesolimbic dopamine system.

Attenuation of the preoperative stress response with midazolam: effects on postoperative outcomes.

Background. Previously, effects of preoperative sedatives were assessed mainly with respect to preoperative outcomes such as anxiety and compliance. The purpose of this investigation was to evaluate the effects of preoperative sedatives on postoperative psychological and clinical recovery. Methods Patients undergoing general anesthesia and outpatient surgery were enrolled in a double-blind, randomized, placebo-controlled trial. Subjects (n = 55) were randomly assigned to receive either 5 mg intramuscular midazolam (n = 26) or a placebo injection (n = 29) at least 30 min before surgery. The anesthetic technique was controlled. Postoperative anxiety, pain, analgesic consumption, clinical recovery parameters, and global health (SF-36) were evaluated up to 1 month after surgery. Results Surgery length did not differ significantly between the treatment and placebo groups (118 ± 45 min vs 129 ± 53 min;P = NS). Throughout the first postoperative week, subjects in the treatment group reported a greater reduction in postoperative pain compared with subjects in the placebo group (F1,50= 3.5;P = 0.035). Moreover, at 1 week, ibuprofen use was reported by less subjects in the treatment group than in the placebo group (0%vs 17.2%;P = 0.026). Subjects in the treatment group also reported a greater reduction in postoperative anxiety throughout the follow-up period (F1,53 = 9.2;P = 0.04). However, global health indexes (SF-36) did not detect any significant differences between the two experimental groups (multivariate F1,45 = 0.44;P = 0.51). Conclusion Subjects treated with midazolam preoperatively self-report improved postoperative psychological and pain recovery. However, the clinical significance of these findings is unclear at the present time.

Sleeping characteristics of children undergoing outpatient elective surgery.

Background A significant number of children undergoing anesthesia and surgery exhibit new-onset sleep-related problems postoperatively. The aim of this longitudinal cohort study was to expand previous research in this area by using a new objective technology. Methods This study compared children undergoing general anesthesia and outpatient surgery (n = 92) to a community-based control group of children (n = 77). Data regarding coping, temperament, anxiety, surgical procedures, and postoperative pain were collected. Subjects underwent actigraphy sleep monitoring for at least 3 nights before surgery and 5 postoperative days (POD). Sleep assessment was performed with actigraphy sleep monitoring and the Post Hospitalization Behavioral Questionnaire (PHBQ). Results Forty-three children (47%) in the surgery group experienced postoperative sleeping disturbances as determined by either the actigraphy or the PHBQ. Only 13 children (14.4%), however, experienced a decrease of at least 1 SD in percentage sleep as assessed by actigraphy. Postoperative pain scores on POD 1 and POD 2 were significantly higher among children who exhibited sleep problems as diagnosed by actigraphy (F = 4.283;P = 0.047). Also, children who exhibited actigraph-based sleep problems scored lower sociability-temperament (14.1 ± 4.3 vs. 17.5 ± 3.4;P = 0.04) scores compared with the community group and had a higher rate of change in their perioperative anxiety levels (group × time interaction, F = 5.1;P = 0.03). Conclusion A significant number of children undergoing outpatient surgery experience postoperative sleep-related problems. The clinical significance of this finding, however, is unclear.

Blocks and bodies : Sex differences in a novel version of the Mental Rotations Test

A novel version of the Mental Rotations Test (MRT) that alternated the standard block figures with three-dimensional human figures was administered to 99 men and 129 women. Women and men differed predictably in their retrospective reports of childhood play and digit ratios, a putative measure of prenatal androgen action. Compared to the block figure items, human figure items on the modified MRT were associated with an improvement in performance in both sexes. However, consistent with the study hypothesis, the enhancing effect of the human figure condition on performance as measured by conventional scores was smaller in men compared to women and not at all evident in men when performance was measured by ratio scores. A closer inspection of the human figures effects on test scores showed performance in women improved for both male and female figure items. In contrast, relative to scores on block figure items, performance in men improved when stimuli were male figures but did not improve when stimuli were female figures. These results add to the evidence that the magnitude of sex differences in scores on the MRT may vary according to the test content and item properties. The findings suggest that online measures of cognitive processing in response to different classes of test stimuli (e.g., animate vs. inanimate objects, self-relevant vs. neutral stimuli) may prove useful in research aimed at understanding the hormonal and social factors contributing to the sex difference in performance on the MRT.

Hormone-behavior associations in early infancy.

The physiological significance of hormonal changes in early postnatal life is emerging, but the behavioral significance in humans is unknown. As a first test of the relationship between hormones and behavior in early infancy we measured digit ratios and salivary hormone levels in forty-one male and female infants (3-4 months of age) who watched a video depicting stimuli differentially preferred by older males and females (toys, groups). An eye-tracker measured visual fixations and looking times. In female infants, hormones were unrelated to visual preferences. In male infants, higher androgen levels predicted stronger preferences for male-typical stimuli. These data provide the first evidence for a role for hormones in emerging sex-linked behavior in early development.