Nanne E. Van De Poll

Gender differences in behaviour: Activating effects of cross-sex hormones

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.

Activating effects of androgens on cognitive performance: causal evidence in a group of female-to-male transsexuals.

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.

Sex-dependent effects of restraint on nociception and pituitary-adrenal hormones in the rat.

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.

Testosterone as appetitive and discriminative stimulus in rats: Sex- and dose-dependent effects

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.

Sex-dependent effects of inescapable shock administration on behavior and subsequent escape performance in rats.

Stress-induced behavioral disturbances have widely been used as animal models of depression. Sex differences, however, have rarely been studied, even though evidence is available to show that males and females react differently after presentation of aversive stimuli. The present experiment investigated the behavioral effects of inescapable shocks on subsequent shuttlebox-escape performance in male and female rats. Exposure to inescapable shocks resulted in suppression of activity during shock administration, which was more severe when shock duration was increased. Females showed less behavioral suppression and they were also more active than males during the adaptation phase, prior to shuttlebox-escape training. Shuttlebox-escape performance was less affected in females than in males compared to that of nonshocked control subjects. Shock duration as a factor only affected efficiency of shuttlebox-escape performance in males.

Sex differences in the effects of inescapable footshock on central catecholaminergic and serotonergic activity

In two experiments sex differences in changes in central noradrenergic, dopaminergic and serotonergic activity were measured immediately after a 30-min session of inescapable footshocks. In Experiment 1 concentrations of noradrenaline, dopamine, serotonin and their major metabolites were determined in the frontal cortex, hypothalamus, amygdala, striatum, mesencephalon and the medulla-pons area. Inescapable shock increased the activity of all 3 transmitter systems, as evidence by increased metabolite concentrations in specific brain areas. Shock-induced increments in metabolite levels were larger in females than in males, especially for the serotonergic system. In addition, shock presentation resulted in a decrement in the noradrenaline content in most areas studied. In the frontal cortex, noradrenaline was reduced by inescapable shock in males but not in females. In Experiment 2, sex-dependent neurochemical consequences of predictable versus unpredictable shocks were studied in the frontal cortex and the medulla-pons area. Similar to Experiment 1, both brain parts showed large shock-induced increments in the activity of the catecholaminergic systems. Differential effects of predictable and unpredictable shock were not found (frontal cortex) or were rather small (medulla-pons) and appeared sex-dependent for serotonin in this area. The sex differences in neurochemical change found in the first experiment were largely replicated in the second experiment. The relevance of the observed sex differences in central neurotransmitter reactivity for sex differences in behavior is discussed.

Anger and aggression in women: Influence of sports choice and testosterone administration

We report on two studies of anger and aggression in women. One study concerns an experimental study of anger induction in aggressive and non-aggressive sportswomen. It was found that sports choice in itself, contrary to expectation, does not predict anger arousal and aggressive behavior in the laboratory. However, at an individual level the anger proneness of the subject, as measured by a questionnaire we developed, was related to the intensity of aggressive behavior and subjectively reported anger. The second study concerns the activating effects of androgens on aggression and anger proneness. In a group of 22 female-to-male transsexuals, a battery of anger proneness and aggression questionnaires was administered twice: shortly before and 3 months after the start of androgen treatment. Administration of androgens was clearly associated with an increase in anger proneness, although there were no changes in several aspects of overt aggressive behavior.

Controllable and uncontrollable footshock and monoaminergic activity in the frontal cortex of male and 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.

Sex- and time-dependent changes in neurochemical and hormonal variables induced by predictable and unpredictable footshock

Previous experiments have revealed sex-dependent effects of inescapable shock in rats. Behavior of male rats was more severely disrupted by inescapable shock than behavior of female rats. These sex differences were found after 1- and 24-hour intervals but not after a 72-hour interval. The present experiment was designed to study various physiological parameters at 1-, 4- and 24-hour intervals after inescapable footshock. The predictability of shock was manipulated by adding a compound light and tone stimulus that preceded shock presentation for one group but was not correlated with shock presentation for another group of subjects. Noradrenaline, dopamine, serotonin, and metabolites of these 3 transmitters were measured in the frontal cortex. Transient shock-induced increments in dopamine and metabolites of dopamine and serotonin were found, but the sex of the animal did not differentially affect this neurotransmitter response. In addition to neurotransmitter concentrations in the frontal cortex, levels of corticosterone were measured in plasma. The pituitary-adrenal axis was activated for a longer period in females than males after shock. The present data do not provide evidence that behavioral sex differences induced by inescapable shock are paralleled by sex differences in neurotransmitter activity. In addition, sex-dependent effects of predictability of shock on neurotransmitter activity were not detected. The relevance of the observed sex-dependent responses in the pituitary-adrenal system is discussed.

Perseverative responding in male and female Wistar rats: Effects of gonadal hormones

Response perseveration was investigated in an experimental procedure which has previously been shown to be sensitive to pharmacologically induced behavioral perseveration and response stereotypy. Different groups of intact, gonadectomized, and gonadectomized plus chronically testosterone-treated male and female Wistar rats were exposed to this procedure in which reinforcers were randomly assigned to one of two levers in an operant chamber. One response on the lever to which the reinforcer was assigned was sufficient to produce a food pellet. Response perseveration, defined as the percentage of trials on which more than one response on the lever not selected for reinforcement was made prior to switching to the selected lever was highest in testosterone-treated subjects. Females made more responses on the lever which had been selected for food on the preceding trial, suggesting that females may be more sensitive than males to the consequences of their behavior. This behavioral difference between the sexes may be mediated by the male hormone testosterone.