Fifty-eight normal cycle, healthy women were confronted with an aversive, anger-provoking situation in the laboratory. Eighteen women were tested in their follicular phase. A further 40 women were tested in the premenstrual phase, half of whom reported suffering from complaints of premenstrual emotional lability and irritation, the other half reported being without premenstrual problems. Apart from a strong effect of emotion induction on cardiovascular arousal and anger-related moods in the follicular and premenstrual groups, a premenstrual phase effect was also demonstrated, with premenstrual women showing evidence of being more affected by the manipulations on systolic blood pressure and intensity of angry behaviour during anger provocation. Furthermore, some differences were found between those subjects who reported suffering from premenstrual complaints and those free of such complaints, among the most interesting ones being differences in cortisol level preceding the experimental session, in intensity of angry behaviour, and in report of anger intensity at debriefing. The study indicates that the premenstrual phase may have the effect of making women more susceptible to responding emotionally to negative life events.

The relative contribution of organizing and activating effects of sex hormones to the establishment of gender differences in behaviour is still unclear. In a group of 35 female-to-male transsexuals and a group of 15 male-to-female transsexuals a large battery of tests on aggression, sexual motivation and cognitive functioning was administered twice: shortly before and three months after the start of cross-sex hormone treatment. The administration of androgens to females was clearly associated with an increase in aggression proneness, sexual arousability and spatial ability performance. In contrast, it had a deteriorating effect on verbal fluency tasks. The effects of cross-sex hormones were just as pronounced in the male-to-female group upon androgen deprivation: anger and aggression proneness, sexual arousability and spatial ability decreased, whereas verbal fluency improved. This study offers evidence that cross-sex hormones directly and quickly affect gender specific behaviours. If sex-specific organising effects of sex hormones do exist in the human, they do not prevent these effects of androgen administration to females and androgen deprivation of males to become manifest.

A role-playing study on anger was conducted in order to identify the influence of sex hormones on individual and gender differences in irritation, anger arousal, and aggression. Different groups were studied: female-to-male and male-to-female transsexuals, with either group tested after 3 months of cross-sex hormone treatment, and untreated control women and men. All subjects were exposed to a 35-min videotape of an individual tested in an aversive, physically stressful, and frustrating situation in the laboratory. While watching, subjects were asked to imagine being in the same situation. Meanwhile, cardiovascular responses were registered and the intensity of moods and aggressive behaviour were assessed. Apart from a clear effect upon cardiovascular arousal and anger-related moods, there were also some interesting differences between the four groups, the most interesting one being a stronger aggressive response in the female-to-male transsexuals. Furthermore, interesting information was gathered with respect to the issue of whether role-playing and actual experimentation provide valid tests of anger and aggression in real life. © 1995 Wiley-Liss, Inc.

The sex-dependent effects of acute restraint (RT) on nociceptive and pituitary-adrenal responses were investigated in the rat. In a first experiment, the effect of 30 min RT on pain sensitivity was evaluated through repeated use of the tail withdrawal test during and after treatment. RT induced an increase in the nociceptive threshold, i.e., analgesia, in males and females, but the duration and time-course of this effect varied between sexes. The latencies returned to approximately control values in females in the second half of RT, but in males they remained higher for the whole period of RT and immediately afterwards. Twenty-four hours later, males displayed longer latencies than controls in response to simple reexposure to the environment. In a second experiment, ACTH and corticosterone plasma levels were measured immediately after 15 or 30 min of RT. ACTH and corticosterone were higher in restrained animals than in controls after both periods of treatment, and in both sexes; however, females showed higher basal and stress corticosterone levels than males. The role played by corticosteroids in the nociceptive responses of the two sexes is discussed.

In the present series of studies existing hostility and anger trait questionnaires were examined. We found them to be unsuitable for our subjects and purpose, A new questionnaire based on novel principles, the Anger Situation Questionnaire (ASQ), was developed to measure anger proneness in women. The ASQ consists of 33 vignettes or scenarios, Each vignette has three dimensions: emotional experience, intensity of emotional experience, and action readiness mode. The ASQ was administered to 146 female students. Out of this sample two extreme groups were selected of 30 subjects each: one group scoring low on self-reported anger and angry readiness, the other group scoring high on both aspects. An anger-induction paradigm was developed consisting of essentially three elements: a physically aversive situation, the performance of some frustrative tasks, as well as an unpleasantly acting female experimenter. The ASQ was validated in this paradigm: subjects scoring high on the ASQ became more angry due to these manipulations; moreover, in most of the subjects at one moment or another a state of anger was induced. © 1994 wiley-Liss, Inc.

It is still unclear whether sex differences in cognitive functioning are mainly due to perinatal organizing effects of sex hormones on the brain, or to activating effects in adulthood. In a group of 22 female-to-male transsexuals a battery of visuospatial and verbal ability tests was administered twice: shortly before and 3 months after the start of androgen treatment. The administering of androgens was clearly associated with an increase in spatial ability performance. In contrast, it had a deteriorating effect on verbal fluency tasks. This study offers preliminary evidence that androgens directly and quickly affect cognitive performance in females.

The present study investigated 1) the importance of the aromatization process during the perinatal period for the development of the sexually dimorphic nucleus in the preoptic area of the hypothalamus (SDN-POA) of male rats, and 2) the relationship between SDN-POA volume and parameters of masculinization in male rats that were treated perinatally with the aromatase-inhibitor ATD. Males were treated with ATD either prenatally or pre- and neonatally, or with the vehicle. Masculine sexual behavior and partner preference were investigated in adulthood. Thereafter, animals were sacrificed and SDN-POA volume was measured. The SDN-POA volume was reduced in both the prenatally and the pre- and neonatally treated group, with a larger reduction in the latter than in the former group. Combined pre- and neonatal ATD treatment resulted in reduced frequency of mounts, intromissions, and ejaculations, as well as a reduced preference for a female over a male. The SDN-POA size was significantly and positively correlated with frequency of masculine sexual behavior, as well as preference for a female over a male.

Male Wistar rats (N = 16) were trained to discriminate 5 micrograms/kg LHRH, injected intraperitoneally, from saline in a two-lever, food-reinforced drug discrimination procedure, with an injection-session interval of 45 min. Reliable discrimination of LHRH was acquired within 60 training sessions. Subsequent generalization tests in brain-cannulated animals showed dose-dependent and time-related partial substitution of intracerebroventricular LHRH for intraperitoneal LHRH (ventricle doses ranged from 25-400 ng, and the injection-session intervals ranged from 10-40 min). These results indicate that centrally administered LHRH may serve as a dose- and time-dependent discriminative stimulus in male rats.

Conditioned place preference, induced by intraperitoneal injections of 5 micrograms/kg luteinizing hormone-releasing hormone (LHRH), was studied by varying the interval between the injection of LHRH and the conditioning sessions. Place preference was investigated for five presession intervals (0, 15, 45, 75, and 120 min) in separate groups of gonadectomized male rats provided with a subcutaneous testosterone implant. It was shown that the presession interval is an important parameter in the development of LHRH-induced conditioned place preference. Place preference was not observed after conditioning with intervals of 0, 75, and 120 min. With 15 and 45 min, however, a reliable preference was induced by LHRH. This study provides insight into the onset and offset of the appetitive stimulus properties of LHRH in male rats.

Local cerebral glucose utilization was investigated in male rats during conditioned sexual arousal. Increased glucose utilization was found in three amygdaloid nuclei after exposure to a stimulus associated with exposure to a sexually active female. No changes were observed in areas known to be of crucial importance for the expression of consummatory aspects of sexual behavior. These results corroborate and extend previous results showing a dissociation between the expression of appetitive and consummatory aspects of sexual behavior at a neural level.

Stimulus properties of subcutaneously injected testosterone were studied in male and female rats. In a conditioned place preference procedure, dose-dependent effects (doses: 0, 0.5, and 1 mg/kg) were observed in males. In females, no place preference could be established (doses: 0, 1, and 3 mg/kg). In addition, 1 mg/kg testosterone acquired discriminative stimulus control in male rats in a taste aversion procedure. Animals injected with this hormone prior to saccharin-LiCl pairings and with its vehicle prior to saccharin-NaCl pairings suppressed fluid intake following the administration of testosterone and not following the administration of the vehicle. Subsequent generalization tests revealed dose-dependent stimulus control of this hormone (range of substitution doses: 0. 125-2 mg/kg). It is concluded from the results that at least pharmacological (supraphysiological) doses of testosterone may act as appetitive stimuli in male rats, but not in female rats. Furthermore, in male rats (pharmacological doses of) testosterone also possess discriminative stimulus properties.

Male and female rats (N = 32) were trained to discriminate 5 micrograms/kg LHRH from saline in a two-lever, food-reinforced drug discrimination procedure with injection-session intervals of 15 min or 45 min. When the interval was 15 min, neither males nor females were able to discriminate the stimulus conditions. With an interval of 45 min, LHRH showed sex-dependent stimulus properties. Male, but not female, rats reliably discriminated LHRH from saline within 50 training sessions. In males, generalization tests showed dose-dependent and time-related stimulus effects of LHRH (doses ranged from 62.5 ng/kg to 8 micrograms/kg, and intervals ranged from -15 min to -120 min). The results indicate that LHRH may be an essential part of the stimulus complex in male rats but could not gain control over operant behavior in female rats.

Effects of controllable and uncontrollable footshock on monoaminergic activity in the frontal cortex and plasma corticosterone levels were studied in male and female rats. Subjects were exposed to a shuttle-box procedure for a period of either 30 min (60 shocks) or 90 min (180 shocks). A shuttle response ended shock presentation for escape subjects, whereas their yoked, same-sex, counterparts were unable to escape from shock presentation. A third group was exposed to the experimental environment, but did not receive any shocks. Concentrations of noradrenaline, serotonin and dopamine and their major metabolites were measured in the frontal cortex by high performance liquid chromatography with electrochemical detection. Plasma corticosterone was measured by radioimmunoassay. Results of this experiment show that: (1) exposure to the experimental environment without shock already increased the activity of all 3 transmitter systems. In particular, serotonin was very responsive to mere confinement to the shuttle-box. Changes induced by exposure to the experimental environment were similar for males and females. (2) Presentation of footshocks further increased transmitter activity. The activation of noradrenaline and dopamine was larger after uncontrollable shock than after controllable shock. Moreover, uncontrollable shock resulted in higher serotonin levels than controllable shock. (3) Sex-dependent effects of controllability were found for noradrenaline and dopamine, but not for serotonin. Differences in catecholaminergic activity between controllable and uncontrollable shock were larger in females than in males. (4) In both males and females, corticosterone levels in plasma were increased by exposure to the experimental environment. A further elevation was found in response to footshock presentation, which was independent of the controllability of shock.

The behavioral effects of exposure to inescapable shocks (IS) were studied in both the holeboard and the elevated plus-maze, 24 and 72 h after IS in male and female Wistar rats. The following effects were observed at the 24-h interval. In both sexes, head-dipping in the holeboard was reduced by IS, whereas general activity (ambulation and rearing) was reduced in males and not in females. Furthermore, the results of a correlation analysis indicate that previous exposure to IS disrupts the dissociation observed in control groups between exploratory activity directed at the holes (head-dipping) and general activity in the holeboard (ambulation and rearing). Effects of IS on plus-maze behavior could be observed in a clear suppression of rearing in males and not in females. IS did not affect time spent on the open arms. At the 72-h interval, IS affected head-dipping in the holeboard only in males and not in females. The present findings show that the effect of IS on specified behavioral elements is sex-dependent, with stronger and longer-lasting effects in males than in females.

Conditioned place-preference induced by intraperitoneal injections of luteinizing hormone releasing hormone (LHRH) was studied in male rats. In Experiment 1, dose-dependent effects (doses: 0, 0.2, 1 and 5 μg/kg) were observed in gonadectomized males provided with a subcutaneous silastic implant containing testosterone. Animals injected with 1 or 5 μg LHRH developed reliable preference for the LHRH-associated compartment of a two-compartment preference box. The 0 and 0.2 μg doses were without effect. Experiment 2 further studied the place-preference effects induced by 5 μg LHRH, by varying the sex steroid baseline condition of the animals. A significant effect of LHRH on place-preference was found in gonadectomized males with a testosterone or estradiol implant and in gonadally intact males. Differences between these groups were not found. However, in gonadectomized males without steroid substitution, LHRH did not induced place-preference. These data indicate that rewarding properties related to LHRH treatment can be observed in male rats, provided that the males are additionally exposed to sufficient levels of circulating sex steroids.

In two experiments, the effects of inescapable shock on subsequent shuttle-box escape performance were studied in male and female rats. Effects of treatment with short-duration shocks (2 s) were studied after 1- and 24-hour intervals (Experiment 1), and effects of long-duration shocks (6 s) were studied after 24- and 72-hour intervals (Experiment 2). Experience with inescapable shock resulted in a serious disruption of escape performance in both males and females. A large increment in escape latencies was found both during fixed ratio 1 and fixed ratio 2 escape training; however, effects of inescapable shock were more pronounced in males than in females. In Experiment 1, sex differences were most obvious after the short 1-hour interval whereas, in Experiment 2, sex differences were only present after 24 hours and not after 72 hours. Shuttle activity during 2-min adaptation prior to shock-escape training was reduced in both males and females treated with IS, and this effect was somewhat stronger in males than in females. The data of these experiments show that male rats are more sensitive to the consequences of exposure to inescapable aversive stimulation than female rats. It is proposed that the time-dependency of the sex differences in behavioral consequences of treatment with inescapable shock may be related to sex differences in transient neurochemical or hormonal changes induced by inescapable shock.

Effects of various doses (0–250 μg/kg, SC) of estradiol-17β (E2) in a two-bottle choice conditioned taste aversion and a two-compartment conditioned place preference procedure were studied in male and female rats. Dose-dependent taste aversion and place aversion effects of E2 were established, and the conditioned taste aversion procedure was found to be more sensitive in detecting aversive properties of E2 than the conditioned place preference procedure. Although aversive properties of E2 were found in both sexes, the effects were clearly more prominent in males as compared to females. From this study, it was concluded that E2 acts as an unconditioned aversive stimulus in both male and female rats capable of gaining control over different types of behavior by associative learning.

Gonadectomized male and female rats were trained to discriminate 50µg/kg estradiol-17B(E(2)) from its vehicle in a one-bottle forced-drinking discriminative taste-aversion procedure. The animals were injected SC with E(2) or arachidic oil, 60min prior to daily training sessions during which they had access to a saccharin (Sac) solution for 10min. Animals injected with E(2) prior to Sac-LiCl pairings and with arachidic oil prior to Sac-NaCl pairings acquired hormone discrimination, only suppressing Sac intake following the administration of E(2) and not following the administration of arachidic oil. Both males and females reliably discriminated E(2) from arachidic oil within 28 training sessions. Subsequent generalization tests revealed dose-dependent stimulus control of Sac intake by E(2) in both sexes (range of substitution doses: 0.4-250µg/kg). The results show that E(2) may act as a discriminative stimulus in male and female rats.