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Biomedical subjects

N E van de Poll

Publications and source records attributed to N E van de Poll.

At least 19 recordsLinked to original sources

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.

Adrenocorticotropic Hormone↗

SDN-POA volume, sexual behavior, and partner preference of male rats affected by perinatal treatment with ATD.

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.

Androstatrienes↗

Studies on long-lasting consequences of prenatal exposure to anticonvulsant drugs.

Based on neonatal examination at birth, it has been estimated that epileptic women have a 2-3 times greater risk of giving birth to an infant with congenital anomalies. But anticonvulsant drugs may also have more subtle influences on the developing foetus which are not visible at birth but only emerge later in life. Evidence for these functional teratogenic influences has been provided by animal research and follow-up studies in young children. This article discusses these findings in human and animal studies. In addition, the outline of a study carried out at the Department of Obstetrics and Neonatology, Academic Medical Centre, Amsterdam, is described. In this study cognitive functioning, fertility and gender role behaviour of young adults, who had been prenatally exposed to barbiturates and/or hydantoins was examined.

Abnormalities, Drug-Induced↗

Cerebral glucose utilization during conditioned sexual arousal.

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.

Amygdala↗

Intracerebroventricular LHRH may serve as a discriminative stimulus in male rats.

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.

Animals↗

Dose-dependent and time-related stimulus properties of LHRH in male but not in female rats.

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.

Animals↗

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.

Animals↗

Estradiol-induced conditioned taste aversion and place aversion in rats: sex- and dose-dependent effects.

Effects of various doses (0-250 micrograms/kg, SC) of estradiol-17 beta (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.

Animals↗

Pituitary and brain beta-endorphin in male and female rats: effects of shock and cues associated with shock.

The present experiment was designed to study whether or not prior exposure to inescapable shock is accompanied by sex-dependent changes in pituitary and central levels of immunoreactive beta-endorphin, which is proposed to play an important role in opioid analgesia induced by aversive stimulation. Further, the effects of brief reexposure (5 min) to the chamber where inescapable shock was experienced earlier, were established in both sexes. Elevated levels of beta-endorphin were found 24 hours after inescapable shock, in the anterior pituitary of males and in the midbrain periaqueductal gray of both males and females. Reexposure to the experimental chamber only affected beta-endorphin levels if shock had been experienced in this chamber. Reexposure after inescapable shock reduced beta-endorphin content of the arcuate nucleus of males and beta-endorphin content of the periaqueductal gray of males and females. The present results are related to previous findings of sensitization and conditioning of analgesic reactions. The sex differences found in the present experiment are discussed with respect to sex-dependent behavioral consequences of inescapable shock.

Animals↗

Luteinizing hormone releasing hormone-induced conditioned place-preference in male rats.

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 micrograms/kg) were observed in gonadectomized males provided with a subcutaneous silastic implant containing testosterone. Animals injected with 1 or 5 micrograms LHRH developed reliable preference for the LHRH-associated compartment of a two-compartment preference box. The 0 and 0.2 microgram doses were without effect. Experiment 2 further studied the place-preference effects induced by 5 micrograms 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 induce 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.

Animals↗

Visual and auditory delayed discriminations in male and female Wistar rats.

Different groups of male and female Wistar rats were exposed to a discrete-trial delayed discrimination procedure, in which subjects were required to discriminate between a continuously or intermittently presented visual (half of the subjects) or auditory (other half of the subjects) stimulus. The opportunity to respond was delayed for 0, 5, 10 or 20 s after stimulus presentation. Both response levers were inserted into the experimental chamber immediately upon the termination of the delay interval. A press on the left lever was followed by food if the continuous stimulus had been presented, while food was presented following a press on the right lever if the intermittent stimulus had been presented. During sessions 1-60, each incorrect response or failure to respond during the 5-s lever presentation was followed by presentation of the same visual or auditory stimulus, and the same delay interval, once the intertrial interval was terminated. This sequence was repeated until a correct response occurred. During sessions 61-90, repeated presentations of the same trial following incorrect responses or a failure to respond on initial trials were no longer presented. All other experimental contingencies remained unchanged. Response accuracy increased with prolonged training. Subjects exposed to the visual delayed discrimination procedure showed less accurate performance than subjects who were exposed to the auditory delayed discrimination procedure. Response accuracy was higher when the delay interval was short than when it was long. Males made more correct responses than females.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Role of noradrenaline in behavioral changes after defeat in male and female rats.

We have tested the effect of noradrenaline depletion by clonidine in agonistic behavior of intact male and gonadectomized testosterone-treated female rats. Animals were subjected to the 'resident-intruder' paradigm: in 4 consecutive daily confrontations residents defeated intruders. Clonidine-treated intruder males showed higher levels of aggression than did their saline-injected controls. In contrast, in females, in which defeat was also followed by reduction of aggression, no effect of clonidine treatment was found.

Aggression↗

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.

3,4-Dihydroxyphenylacetic Acid↗

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.

Animals↗

Operant conditioning of response variability in male and female Wistar rats.

It has previously been suggested that some of the behavioral differences between the sexes in food motivated operant procedures may be a function of the fact that males are more likely than females to exhibit stereotyped behavior. If such is the case, then it might be expected that behavioral variability is more easily conditioned in females than in males. The present experiment was designed to investigate this notion. Male and female Wistar rats were trained to respond in a procedure in which response variability was explicitly reinforced. In this procedure subjects had continuous access to two response levers in the experimental chamber. In the first experimental condition, each sequence of four responses was followed by the presentation of a food pellet, if the sequence differed from the two sequences which preceded it (Lag 2). Time-out was presented when such was not the case. During time-out the levers were retracted from the chamber and all stimulus lights were extinguished for 4 sec. In subsequent experimental conditions, subjects had to produce four-response sequences which differed from the preceding four, eight and sixteen sequences respectively (Lag 4, 8, 16). Response sequences were classified by the number of switches between levers. Behavioral variability increased as the lag requirement was increased, showing that variability is a conditionable dimension of behavior. Differences between males and females were however not observed. These results thus contradict the previously reported finding that males exhibit more behavioral stereotypy than females. It is suggested that procedural variables may account for these seemingly contradictory findings.

Animals↗

Lesions of the SDN-POA inhibit sexual behavior of male Wistar rats.

Discrete bilateral lesions in the SDN-POA of sexually naive adult male rats were found to decrease the number of animals ejaculating and/or to increase latencies to the first mount, intromission and ejaculation. The deleterious effects of the lesions disappeared after 4 tests for sexual behavior but were reinstated when the males were tested under suboptimal conditions, i.e., when they were tested with a marginally receptive female or when they had only limited access to the stimulus female. It was subsequently shown that males with a bilaterally lesioned SDN-POA still showed an increase in plasma testosterone. LH and prolactin levels in response to sexual stimulation. Effects of the lesions on scent marking were not found. Together with previous data indicating that SDN-POA-lesions disrupt masculine sexual behavior in females, these data are taken as evidence that the SDN-POA plays a role in the regulation of masculine sexual behavior. The data further suggest that previously reported negative results of SDN-POA-lesions on masculine sexual behavior in male rats might be attributed to the use of sexually experienced instead of sexually inexperienced animals.

Animals↗

Sexual behavior and sexual orientation of the female rat after hormonal treatment during various stages of development.

The amount of circulating sex steroids during Postnatal Days 30-90 was varied in normally developed and in androgenized female rats. The influence of these manipulations on sexual behavior and sexual orientation was investigated. Normally developed or neonatally androgenized females were ovariectomized and implanted with estradiol through Postnatal Days 30-90 or sham-implanted. The remaining subjects were left intact during that period. The hormonal condition during Postnatal Days 30-90 significantly affected the behavior of normally developed females, but affected the behavior of neonatally androgenized females only to minor extent. Estrogen implants in normally developed females enhanced masculine sexual responses and induced a female-directed sexual orientation. Feminine sexual responses were unaffected by this treatment. Sham-implanted, normally developed females showed a male-directed sexual orientation and fewer masculine sexual responses than subjects which were left intact during Postnatal Days 30-90. Neonatal androgen treatment in general resulted in elevated levels of masculine Neonatal androgen treatment in general resulted in elevated levels of masculine sexual responses, inhibited feminine sexual behavior, and facilitated a female-directed sexual orientation.

Animals↗

Sex differences in passive avoidance behavior of rats: sex-dependent susceptibility to shock-induced behavioral depression.

Male and female Wistar rats were trained in a standard passive avoidance task. One-half of the subjects was shocked (S) upon entering a dark compartment, the other half was not (NS). One hour after S and NS experience subjects were tested. During testing different behavioral elements were observed in order to elucidate the variables which might be responsible for the observation of sex differences in passive avoidance behavior (Experiment Ia). In addition, separate groups of NS and S male and female rats were used to establish effects of sex and shock presentation on locomotor activity (Experiment Ib). One hour after S and NS experience within a passive avoidance procedure these subjects were tested for open field ambulation. Results of both experiments indicated that shock-stress reduces locomotor activity of male and female rats, but to a lesser extent in female rats. Sex differences in behavioral responses to aversive stimuli may thus be a consequence of a sex-dependent susceptability to stress-induced behavioral depression.

Animals↗