Effects of losing and testosterone upon subsequent behavior in male and female S3 (Tryon Maze Dull) rats

Attempts were made to determine whether modification of agonistic behavior by experience differs in the sexes and if so, whether testosterone is involved in this response. Gonadectomized male and female CPB-S3 (Tryon Maze Dull) rats were treated with testosterone propionate (TP, 250 μg) or vehicle and subjected to tests in which they became either winners or losers. S3 males and females were tested against Long Evans rats to become losers or against Wistar rats to become winners. Subsequently, S3 winners were tested against losers. In addition, winners and losers were tested against naive S3 opponents of the same sex. After varied agonistic experiences, all animals were tested for social preference in a situation in which they could choose between their respective opponents without the possibility of social interaction. Thereafter, they were also exposed to a two-choice passive avoidance learning procedure to see if the behavioral effects of aggressive interactions generalized to nonsocial learning. Males and females reacted differently to winning or losing, the presence of testosterone being a critical factor in the manifestation of this sex difference. Relatively permanent effects on aggressive and other behaviors were only established in TP-treated males. Losing experiences in the social-preference test generally led to a slight preference for naive, less aggressive animals. Testosterone-treated male losers, the group expected to be most vulnerable to generalized inhibition and impairment of learning, did not differ from other categories in the two-choice passive avoidance procedure, although marked differences were observed between the sexes and between testosterone and oil-treated animals.     

Effects of neonatal treatment with 1-(2,5-dimethoxy-4-lodophenyl)-2 aminopropane HCI (DOI) and ritanserin on agonistic behavior in adult male and female rats

The role played by the neonatal 5-hydroxytryptamine (5HT) system in the organization and sexual differentiation of adult agonistic behavior was investigated in rats. Focus was on the 5HT2 receptor subtype, which has been demonstrated to be involved in agonism control in the adult. 5HT2 activity was experimentally manipulated by administration of a specific agonist [1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI)] or antagonist (ritanserin) during the second week of life, when serotonin is known to concur to anatomical and behavioral sexual differentiation. Interactions between early 5HT2 activity, genetic sex, and neonatal circulating testosterone (T) were studied by administering the ligands to males, females, and androgenized females. At adulthood, the animals were tested for both aspects of agonism, i. e., aggression and defense, in a 20-min confrontation with an unfamiliar conspecific of the same sex, age, body weight, and social experience. Neonatal administration of the 5HT2 antagonist ritanserin increased aggression independently of sex; it also increased defense, but this effect was confined to males. The agonist DOI had no effect on aggression, but enhanced defense in males and androgenized females, with an effect which depended therefore more on neonatal T than genetic sex. Females appeared in general less sensitive to neonatal 5HT2 manipulation than both androgenized females and males; this suggests that neonatal T is crucial for experimental modifications of neonatal 5HT2 activity to have any consistent effect on adult agonistic behavior. On the other hand, effects observed in males and androgenized females were dependent on the behavior considered and the drug administered. This was especially evident for defense, enhanced by ritanserin in males only, and in both males and androgenized females by DOI. Neonatal 5HT2 activity seems therefore to play a role in the modulation of adult agonistic behaviors, which depends on the behavior considered and is under multiple control of genetic sex and hormonal neonatal substrate. © 1994 Wiley-Liss, Inc.     

Reversal of Long-Delay Conditioned Taste Aversion Learning in Rats by Sex Hormone Manipulation

Conditioned taste aversion (CTA) learning is an adaptive, robust, well-established learning and memory paradigm. Strong taste aversions develop to the conditioned stimulus (CS = saccharin) despite long delays between exposure to the CS and unconditioned stimulus (US = LiCl). Rats display a sexually dimorphic pattern of long-delay CTA learning (Foy et al., 1996). The present study examines whether this sex difference is a result of activational or organizational hormone action, because here we implanted gonadectomized rats with their normal hormone replacements, or with opposing hormones prior to testing in a 4-hr delayed CTA learning task. We found that gonadally intact male rats displayed a more robust CTA response than intact female rats. Gonadectomy essentially eliminated this sex difference; gonadectomized males and gonadectomized females displayed similar CTA responses. In gonadectomized rats, when their normal sex hormones were replaced with implanted hormone pellets, the sex difference in CTA learning was reinstated. In contrast, when gonadectomized rats were implanted with opposing hormones, the sex difference was reversed. Gonadectomized female rats implanted with 5alpha-DHT pellets (metabolite of testosterone) displayed a stronger CTA response compared to gonadectomized males implanted with 17beta-estradiol pellets. Regardless of the original developmental hormonal environment, our study suggests that an activational manipulation of circulating hormones serves to significantly influence long-delay CTA learning in rats.     

Reversal of long-delay conditioned taste aversion learning in rats by sex hormone manipulation

Conditioned taste aversion (CTA) learning is an adaptive, robust, well-established learning and memory paradigm. Strong taste, aversions develop to the conditioned stimulus (CS=saccharin) despite long delays between exposure to the CS and unconditioned stimulus (US=LiCl). Rats display a sexually dimorphic pattern of long-delay CTA learning (Foy et al., 1996). The present study examines whether this sex difference is a result of activational or organizational hormone action, because here we implanted gonadectomized rats with their normal hormone replacements, or with opposing hormones prior to testing in a 4-hr delayed CTA learning task. We found that gonadally intact male rats displayed a more robust CTA response than intact female rats. Gonadectomy essentially eliminated this sex difference; gonadectomized males and gonadectomized females displayed similar CTA responses. In gonadectomized rats, when their normal sex hormones were replaced with implanted hormone pellets, the sex difference in CTA learning was reinstated. In contrast, when gonadectomized rats were implanted with opposing hormones, the sex difference was reversed. Gonadectomized female rats implanted with 5α-DHT pellets (metabolite of testosterone) displayed a stronger CTA response compared to gonadectomized males implanted with 17β-estradiol pellets. Regardless of the original developmental hormonal environment, our study suggests that an activational manipulation of circulating hormones serves to significantly influence long-delay CTA learning in rats.     

Organisational effects of neonatal and pubertal testosterone on sexually differentiated behaviours in the open-field and head-dip apparatus

On days 1 and 4 after birth rats were injected with 100 μg of testosterone propionate (TP) or vehicle, and at 35 days of age they were injected intramuscularly with 400 μg of testosterone oenanthate (TO), a long acting androgen, or the vehicle. There were four groups (oil-oil, TP-oil, oil-TO, TP-TO), each group subdivided by sex. Females treated with testosterone neonatally or at puberty were masculinised or defeminised on adult open-field behaviours, being less active and rearing less than oil-oil females; the oil-TO group also defaecated significantly more than controls. The TP-TO female group was indistinguishable from the oil-TO group. In a second experiment, sex differences were found in head-dipping behaviour as well as in activity and rearing. Females treated with TP or TO reared less and defaecated more than controls, and TP also decreased activity, but neither hormone treatment affected head-dipping behaviour. There is thus a peripubertal as well as a neonatal period when testosterone can act organisationally to masculinise or defeminise female rats. Potentiation between effects of neonatal and pubertal androgens was found on female body weights. TO alone had no effect, but TP-TO females were significantly heavier than controls at 90 days of age and by 130 days of age the TP-oil group was also heavier than controls.     

Digit ratio and faculty membership: Implications for the relationship between prenatal testosterone and academia

Digit ratio (length of index finger divided by length of ring finger) is an index of exposure to prenatal testosterone. Prenatal testosterone slows the growth rate of the left side of the brain while enhancing growth of the right side. Right hemisphere processing is associated with better visual‐spatial and mathematical abilities, as is digit ratio. Thus, traditional sex differences in visual‐spatial and mathematical abilities can be attributed to differences in exposure to prenatal testosterone, indexed by a sex dimorphic pattern in digit ratio (female=1.00, male=0.98 for UK samples). Additionally, the digit ratio is a marker for within‐sex variance in visual‐spatial ability. This study examines the digit ratio of an academic sample. No sex differences are found and there is a significant difference between the Science Faculty and Social Science Faculty. Social Scientists of both sexes have a ratio consistent with the male norm (0.98) whilst Scientists have a digit ratio consistent with the female norm (1.00). These results are discussed in terms of the lower normal range of male testosterone being associated with highest visual spatial abilities. Relationships with fertility and Dyslexia are also identified.     

Personality profiles at various levels of athletic participation

Various grades of athletes (265 male and 134 female) were administered the German version of the EPQ. The entire group was characterized by being more extraverted and less neurotic (compared to population norms); sex differences were exhibited, female profiles being higher on emotionality and lower on Psychoticism (tough-mindedness) with no significant difference being observed in mean Extraversion scores. When grouped in terms of ‘level of competitive involvement’, top-class male athletes were shown to be significantly more tough-minded and less stable than middle- or lower-class participants, an almost opposite trend being found in females, where top athletes were liable to be more extraverted, less neurotic and less aggressive and tough-minded than the other classes.     

Hormonal control of sexual attraction in pseudohermaphroditic female dogs

Groups of female dogs exposed to different degrees of androgenic stimulation during development and a control group of ovariectomized females were tested for their attraction to tethered male and female stimulus animals. Attraction to the male was measured before and after administration of estradiol, and attraction to an estrous female was tested before and after administration of testosterone propionate (TP). Time spent visiting the tethered male was approximately equal for all groups prior to hormone treatment, but after receiving estradiol, control females exhibited a pronounced increase in visiting time; the second longest visits were paid by females that had received moderate amounts of androgen before birth; more heavily androgenized females exhibited no increase in attraction to the male despite estradiol injections. Visits to the estrous female before administration of TP were longer for some groups than for others, but there was no relation between the degree of perinatal androgenization and mean visiting time. After injections to TP the most pronounced increase in visiting was shown by females that had received the largest amounts of androgen during development, and the second largest increase occurred in the prenatally androgenized group. Control females showed the smallest increase in visiting time.     

Male-female differences and the influence of neonatal and adult testosterone on intraspecies aggression in rats.

Male and female albino rats were tested for intraspecies aggression without the use of shock. In the first experiment, male pairs showed more biting attacks, offensive sideways movements, and self-grooming than did female pairs; male pairs also showed more stereotyped defensive/submissive behaviors and were wounded more frequently. The second experiment examined the effects of neonatal castration and testosterone propionate (TP) administration on fighting. Males castrated at birth attacked other males less frequently than did controls when tested with TP treatment as adults. The TP given at birth to neonatally castrated males restored attacks to control levels. Females given TP as neonates did not differ from either male or female controls. Other aggressive/defensive behaviors, however, did not show this pattern. The results suggest that while the presence of testosterone during a brief postnatal period and during adulthood is necessary for attack behavior to occur, other related behaviors may not be affected in a similar manner.     

Noninvolvement of testosterone in aggressive defense behavior in the male blind mole rat Spalax ehrenbergi

Blind mole rats (Spalax ehrenbergi) are solitary and aggressive subterranean rodents. Aggressive defense behavior in the mole rat functions to deter neighboring competitors from territory, food, and mates and includes seismic and odor signals. The aim of the present study was to determine whether the aggressive defense behavior displayed by male mole rats is testosterone dependent. Five behavioral variables were taken as being representative of such aggressive interaction: exposing teeth, biting, bulldozing movements of the head, soil blocking, and self‐grooming. We monitored male testosterone levels and aggressiveness throughout the annual cycle, which can be divided into three main climatic periods: cold and rainy (September–February); warm, during which the soil is still moist and easily excavated (March–May); and hot (June–August), when the soil is hard and dry. In a second experiment the effect of endogenous and exogenous testosterone on male aggressive defense behavior was determined before and after castration and following testosterone propionate replacement. We found fluctuations in male testosterone concentrations, with three peaks: in November, May, and August, one in each of the three climatic periods. However, these fluctuations did not correlate with male aggressive behavior, which remained constant throughout the year. Furthermore, because neither castration nor testosterone propionate replacement in castrated individuals affected their defense behavior, we suggest that such behavior in male mole rats is testosterone independent. The continuous excavation and maintenance of the mole rat’s underground tunnel system demands high energy expenditure year‐round and constant defense of territory sites and food caches from intraspecific rivals. Thus, although testosterone may fluctuate as a result of seasonal breeding cycles, constant high levels of aggressive defense throughout the year are crucial for the survival of the male mole rat in its solitary subterranean environment. Aggr. Behav. 27:64–72, 2001. © 2001 Wiley‐Liss, Inc.     

Evaluation of prenatal androgen and ovarian secretions on receptivity in female and male rats

Offspring of rats infected daily from Day 16 through Day 20 of gestation with either 2 mg of testosterone propionate (TP) in .1 ml of sesame oil or oil alone were tested for sexual receptivity following injections of 3.3 microgram of estradiol benzoate (EB) and .5 mg of progesterone (P) beginning at 40, 80, or 120 days of age. At each age, neonatally gonadectomized males and females from TP-injected litters exhibited less receptivity than corresponding oil-injected controls. Prenatally androgenized females were similar to neonatally castrated oil-injected males at all ages. Ovarian implants from birth to 35 days of age significantly increased receptivity in neonatally castrated males and androgenized females. Increasing the age at which testing was initiated systematically reduced receptivity in all groups.     

Salivary testosterone and self-report aggressive and pro-social personality characteristics in men and women

Measures of salivary testosterone and the personality dimensions of aggression and pro-social behavior were obtained in 306 (155 male and 151 female) university students. Each participant provided two samples of saliva and completed ten self-report personality scales from multiple inventories. A factor analysis of the personality scales produced two factors, an aggression factor and a pro-social behavior factor. Men averaged five times the amount of salivary testosterone as women (99 pg/ml vs. 18.5 pg/ml) and rated themselves as more aggressive and less nurturant. Within each sex, testosterone was positively correlated with aggression and negatively correlated with pro-social personality. Structural equation modelling analyses suggested that a direct effect model best described the relationship between salivary testosterone and the latent personality dimensions of aggression and pro-social behavior. © 1996 Wiley-Liss, Inc.     

Neonatal androgenic stimulation and adult sexual behavior in male and female golden hamsters.

Neonatally and adult castrated male hamsters as well as neonatally androgenized and nonandrogenized female hamsters were tested for both mounting and lordosis behaviors during treatment with either testosterone or ovarian hormones. Neonatal androgenization facilitated mounting behavior in adult animals administered either testosterone or ovarian hormones and suppressed lordosis behavior in adult ovarian-hormone-treated animals. Early androgen effects on the display of lordosis behavior during adult testosterone treatment were complex and varied with the exact timing of perinatal endogenous or exogenous androgenization. Species differences in hormone-behavior relationships and the possible role of perinatal androgenization in the development of rodents' ability to aromatize androgens were discussed.     

Sex reversal in female Betta splendens as a function of testosterone manipulation and social influence

In Experiment 1, female Betta given daily injections of testosterone (T) for 9 weeks acquired anatomical features characteristic of males as indicated by changes in fin length, body coloration, and gonadal morphology. These findings suggested that a potential for sex reversal exists in females of this species. In Experiment 2 we measured changes in aggressive behavior during testosterone-induced anatomical changes. Aggression decreased toward females and increased toward males as treatment with T progressed. The final displays of aggressive behavior and anatomical characteristics of fish injected with T resembled those of typical males. In Experiment 3, female Betta primed with T injections for 3 or 6 weeks and permitted to interact socially with females continued to display characteristics of sex reversal after T supplementation ceased. Sex reversal in isolated fish injected with T for 3 or 6 weeks was not sustained, and fish receiving only the control vehicle showed negligible change in both the isolated and community conditions. We discuss the results in terms of similarities with the sex change process found in isolated communities of coral reef fish.     

Role of neonatal androgens in sexual differentiation of brain structure, scent marking, and gonadotropin secretion in gerbils

Gerbils display a sexually dimorphic scent marking behavior that responds to testosterone (T) in adulthood and develops under the influence of testosterone perinatally. A complex of cell groups between the preoptic area and anterior hypothalamus of the gerbil brain is also sexually dimorphic and responsive to testosterone. One of these cell groups, the sexually dimorphic area pars compacta (SDApc), usually exists only in males. Even when given testosterone, adult female gerbils rarely have an SDApc. To determine if the SDApc develops under the influence of testosterone, male gerbils were castrated or given sham operations on the day they were born or 1 day later, or were not manipulated. Female gerbils were injected subcutaneously with 0, 50, or 100 micrograms testosterone propionate (TP) on the day after birth. When given ovarian transplants as adults, neonatally castrated males scent marked at low levels typical of females. Neonatally androgenized females given testosterone as adults scent marked at high levels typical of males. Neonatal castration did not affect the probability that the SDApc would develop, but neonatal androgenization did. Half the females given either dose of TP as neonates had SDApcs bilaterally. The sizes of the SDApcs present in females depended on the dose of testosterone given neonatally. The larger dose produced larger SDApcs. The 100-micrograms dose of TP also defeminized gonadotropin secretion, but the 50-micrograms dose did not. The castration of males neonatally prevented the defeminization normally caused by endogenous testosterone. Both groups of neonatally castrated males formed corpora lutea in their ovarian transplants, but control males did not.     

Maternal aggression in mice and rats towards male and female conspecifics

Although postpartum aggression is primarily studied in laboratory mice and rats, it is unclear how the two species compare in terms of the factors associated with peak levels of aggressive behavior. Using the same experimental protocol, we assessed the relative effect of intruder sex and time since parturition on the frequency of maternal aggression in Long-Evans rats and CFW mice. Females were studied for 2 consecutive cycles of pregnancy and lactation. During the first lactation, aggression was tested 2 times per week for 3 weeks in order to select animals that attacked at least once. During the second lactation, both pup care and aggressive behavior were assessed in detail. Testing occurred twice in each lactation week, with postpartum days 1–7, 8–14, and 15–21 considered weeks 1, 2, and 3, respectively. Maternal behavior towards 3 pups was observed for 5 minutes, followed by a confrontation with an intruder. Lactating females encountered female intruders once per week, and male intruders in the alternate weekly test. The same behaviors were measured in the 2 species, except for the tail rattle exhibited by mice and the aggressive posture shown by rats. Lactating rats and mice show similar decreases in pup care behavior as lactation progresses in time; yet the factors associated with peak levels of aggression differ between species. In Long-Evans rats, female intruders receive more attacks, threats, and aggressive postures than males. Frequency of attack bite and sideways threat declines in each passing week of lactation. Lactating mice are more aggressive toward male intruders throughout the lactation period. Mice still attack and threaten during the third week of lactation, but less often in comparison to the first week. Therefore, peak levels of aggression vary in mice and rats both as a function of intruder sex and lactation week.     

Effects of Early Maternal Separation on Subsequent Reproductive and Behavioral Outcomes in Male Rats

To investigate effects of maternal separation on reproductive and behavioral outcomes, male Wistar rats were separated from their mothers daily for 3 hr (maternal separation; MS) or 0 hr (control) from postnatal day (PND) 1 to 14. Timing of puberty, reproductive parameters, hormone levels, and aggressive behaviors in juvenile and adult rats were examined. Contrary to expectations, there was no effect of maternal separation on any measure of aggression. However, maternal separation altered peripubertal testosterone secretion and increased mean day of preputial separation. In addition, adult MS males demonstrated less total sexual behavior. There was no difference in sperm counts or testosterone levels at necropsy on PND 56 or in adulthood, but seminal vesicle weights were increased in adult MS rats. These results suggest that early life stress may influence hypothalamic-pituitary-gonadal axis development in males, at least during peripuberty.     

Age- and sex-related induction of excessive grooming and "wet-dog" shakes by the codeinone RX 336-M in the rat

Peripheral administration of the dihydrocodeinone RX 336-M (6 mg/kg) stimulated vigorous "wet-dog" shakes and excessive grooming in young drug-naive rats. The effects of RX 336-M were greater in younger than in older animals of both sexes, and were greater in 39-day-old male rats than in female rats of the same age. In a second experiment, female rats were pretreated with testosterone benzoate (1 mg/kg/day) for 1 week prior to testing the effects of RX 336-M at 39 days of age. The sex hormone pretreatment enhanced the ability to RX 336-M to induce "wet-dog" shakes and excessive grooming in female rats. The results suggest that both sex- and hormone-dependent developmental status are critical in the display of the so-called "quasi-morphine withdrawal syndrome." The results imply, and are consistent with previous studies which suggest, that different neural mechanisms underlie the behavioral responses induced by ACTH and RX 336-M.     

The role of endocrines in isolation-induced lntermale fighting in albino laboratory mice. II. Sex steroid influences in aggressive mice

Isolation-induced intermale fighting in laboratory mice can be dramatically reduced under most circumstances by castration. This behavior in castrates may, however, be restored, or even accentuated, by androgen replacement. Experiments on the effects of sex steroids on such fighting in castrated mice, which, for want of a better term, are designated as “aggressive,” have been recently described. These mice are housed with a female until 10 days after siring a litter and are, thereafter, housed individually for a further 14 days before castration and subsequent hormone treatment. Such mice show substantial levels of fighting in “standard-opponent” tests even before isolation. Although castration results in reduced fighting in these mice, this behavior is rarely completely abolished in all individuals. It seems likely that steroid treatment of aggressive mice maintains or intensifies an already present motivation. Treatments in these studies consisted of daily oil-based intramuscular injections for 14 days preceding and throughout behavioral testing. The standard-opponent tests were 7 min encounters with adult, subordinate, grouped males in the cleaned home cages of experimental mice. The steroids investigated included estradiol benzoate (EB), 19-hydroxytestosterone (19-OHT), androstenedione (A), testosterone (T), and Sα-dihydrotestosterone (DHT), either singly or in combination. The results suggest that (a) on a dosage basis, estrogens were at least as effective as androgens in maintaining fighting in castrated aggressive mice; (b) 19-OHT (one of the metabolic intermediates between testosterone and 17 β-estradiol) was also effective but somewhat less so than the same dose of EB; (c) the three naturally occurring androgens investigated all effectively maintained fighting at comparatively low doses (50 μg/day) which compares with a replacement dose of 500 μg/day of T in some studies in traditional castrated mice (e.g., Luttge and Hall, 1973); (d) aromatization is not essential for a behavioral action of androgens as DHT, a nonaromatizable androgen, maintained fighting in these mice; (e) whereas a two-site (central motivational and peripheral penile) action seems probable in the influence of androgens on sexual behavior in castrated rats (e.g., Parrott, 1975), DHT did not augment the action of EB on fighting in castrated aggressive mice, indicating that only a central action of steroids was required in the aggressor.