Sex-dependent effects of neonatal inflammation on adult inflammatory markers and behavior.

Inflammatory molecules, such as cyclooxygenase (COX), a prostaglandin synthetic enzyme, have been identified as a marker of depressive symptomology. Previously, we have observed elevated basal COX-2 expression in the hypothalamus of adult male rats treated neonatally with lipopolysaccharide (LPS), which might suggest a phenotype for disrupted hedonic behavior, a symptom of depression. However, COX-2 and its contribution to the expression of anhedonic behavior has not been investigated in these males or in female rats across the estrous cycle, which is the purpose of the current work. Here, we examine the effects of a neonatal LPS challenge or saline on the sucrose preference test as a measure of anhedonia, and hypothalamic COX-2 expression, in adult male and freely cycling female rats. Our data indicate a sex difference in that neonatal LPS at postnatal d 14 causes elevated basal expression of hypothalamic COX-2 in male, but not in female, rats. Additionally, baseline sucrose preference in male and female rats was unaltered as a function of neonatal LPS treatment or estrous cycle stage. In both male and female animals, 50 microg/kg LPS in adulthood caused elevated plasma IL-6 and hypothalamic COX-2 expression in neonatally saline-treated rats but significantly less so in neonatally LPS-treated rats of both sexes; this neonatal programming was not evident for sucrose preference or for total fluid intake (even after much higher doses of LPS). Our data are suggestive of a dissociation between inflammation and anhedonic behavior and a differential effect of neonatal inflammation in males and females.

Sex differences in catalepsy: evidence for hormone-dependent postural mechanisms in haloperidol-treated rats.

Catalepsy, a symptom of Parkinson's disease and related disorders can be produced in rats and other laboratory animals by the blockade of nigrostriatal dopamine using dopaminergic antagonists such as haloperidol. When haloperidol-induced cataleptic rats are placed facing downward on an inclined plane, they will brace against the resulting downward force by pushing backwards, and if they lose postural stability, or their position on the inclined plane, they will jump forward. Females, however, jump from the inclined plane at a significantly lower angle than do males. Frame-by-frame analysis of the jumping sequences revealed that females and males use a different combination of postural adjustments to maintain their position on the inclined plane prior to jumping. Furthermore, gonadal hormone manipulations at birth and in adulthood reveal that these sex differences in postural adjustments are dependent on the organizational effects of gonadal hormones in the perinatal period. These results provide evidence for sex differences in postural support mechanisms and suggest that the sex of subjects, or their hormonal state, must be considered when studying the behavioral aspects of neurological disorders such as Parkinson's disease which include a postural component.

The development of a sex-differentiated defensive motor pattern in rats: A possible role for juvenile experience.

When protecting a food item held in the forepaws, rats will dodge laterally away from an approaching conspecific. Both males and females dodge, but do so differently, with females pivoting around the pelvis and males pivoting around the midbody. While females tend to end the dodge with their rumps opposing the other rat's midbody, males typically oppose the head. In this study, two developmental factors were investigated for their role in the genesis of this sex-differentiated motor pattern: (a) Dodging by males and females was analyzed before and after puberty to ascertain whether the differential pattern of movement was associated with the pubertal change in pelvic morphology, and (b) Dodging by adult males and females that had been raised without social interaction from weaning was analyzed to ascertain whether experience in the juvenile phase of development was necessary. In both studies, males and females performed the sex-typical version of the dodging motor pattern regardless of age or test condition. However, orienting to the head of the opponent was disrupted in males reared in social isolation, a feature of dodging that developed between weaning and puberty. Therefore, the evidence is consistent with the view that while the sexual differentiation of the motor organization of dodging develops without the need for experience, the males' ability to direct this motor pattern with the correct orientation towards the opponent requires some prepubertal experience.

A kinematic analysis of sex-typical movement patterns used during evasive dodging to protect a food item: the role of testicular hormones.

Feeding rats dodge laterally away from a conspecific attempting to steal their food. Dodges by female and male rats differ in their composition of movement. Females pivot around a point more posterior on the longitudinal axis than do males, producing a greater amount of movement of the snout in relation to the pelvis. This experiment examined the role of testicular hormones on these sex-typical movement patterns. Castration at weaning (21 days) does not affect the male-typical pattern. Neonatal testicular hormone manipulation, however, does alter sex-typical patterns of movements. Whereas castration neonatally makes male rats more female-like, injections of neonatal female rats with testosterone propionate make them more male-like. These findings suggest that the organization of sex-typical patterns of dodging involves perinatal action of gonadal hormones. Results are discussed in relation to anatomy, neural structure, and the role of gonadal hormones during development.

Multiple differences in the play fighting of male and female rats. Implications for the causes and functions of play.

Play fighting is the most commonly occurring form of social play in juvenile mammals. Typically, males engage in more play fighting than females, and this difference has been shown to depend on the action of androgens perinatally. It is generally believed that the differences in play fighting between the sexes are quantitative and do not involve qualitative differences in the behavior performed. We show that this is an incorrect characterization of sex difference in play fighting. For example, in laboratory rats, there are at least five different mechanisms that contribute to the observed sex differences in play fighting. These mechanisms involve (I) the motivation to initiate play, (II) the sensory capacity to detect and respond to a play partner, (III) the organization of the motor patterns used to interact with a partner, (IV) age-related changes at puberty in initiating play and in responding to playful contact, and (V) dominance-related changes in adulthood in the pattern of playful interaction. Sex differences in the play fighting of rats are due to an interaction of all of these mechanisms, some of which are sex-typical not play-typical, and involve both quantitative and qualitative differences. This is clearly different from the prevailing view that play fighting is a unitary behavior which is masculinized perinatally. Indeed, even though all five mechanisms are androgenized perinatally, the sensorimotor differences also involve defeminization (i.e. reduction of female-typical qualities). This expanded view of the mechanisms contributing to the sex differences in play fighting has implications for both the analysis of the neural systems involved, and for the functional significance of this activity in childhood and adulthood.

A kinematic analysis of evasive dodging movements used during food protection in the rat (Rattus norvegicus): evidence for sex differences in movement.

Food-deprived rats (Rattus norvegicus) will protect their food by dodging away from a conspecific. A detailed kinematic analysis of these movements in adult rats shows that each sex uses sex-typical movements. Females move their snout through a greater spatial curvature, and their snout achieves a greater velocity, relative to the pelvis, than males. Males make more hindpaw steps than females and achieve a more simultaneous movement of the fore- and hindquarters. This suggests that females pivot around a point more posterior on the body than males. The finding that functionally similar patterns of movement have a sex-specific organization provides a new dimension for the study of sex differences. These differences are discussed in relation to sex differences in sex-typical behaviors, associated body structure, and neural control.

Uses of vision by rats in play fighting and other close-quarter social interactions.

Enucleated juvenile rats were compared to sighted juveniles, and tested over six trials. In some of these trials, the vibrissae were clipped and the test chamber was flooded with white noise. Even though the enucleated rats played, they did so in an atypical manner. They tended to initiate more playful and other social contacts, and were more likely to defend themselves if contacted. When they did defend themselves, they adopted behavior patterns that were more likely to evade the partner's attack. In addition, the enucleated rats were hypersensitive to the partner, being more likely to respond defensively when contacted further from the nape (the main play target). All these changes in play fighting by nonsighted rats suggest that the loss of vision leads to motivational changes in activity and reactivity, and so has an indirect effect on play behavior. In addition, direct evidence is also provided to show that vision is used to orient attacks to the nape. When the vibrissae were closely clipped, the sighted rats continued to make direct attacks on the partner's napes, whereas the nonsighted rats did not. Rather, they first contacted some other part of the partner's body and then oriented to the nape. Another test paradigm was used to determine whether vision is used to trigger defensive responses. The rats were partially food deprived as adults and were filmed in a food wrenching and dodging situation where one rat was given a food pellet and the other allowed to steal it. Measurement of the distance at initiation of the lateral swerve away from the approaching partner (i.e., dodge) showed that when the vibrissae are clipped, the sighted rats continued to initiate dodges at the same distance, whereas the nonsighted rats could not. Therefore, vision appears to have an active role in organizing movement sequences of attack and defense in play fighting and other close-quarter interactions.

Differential effects of amphetamine on the attack and defense components of play fighting in rats.

Treatment with d-amphetamine has been shown to cause a decrease in play fighting by juvenile rats. Previous studies, however, did not determine if all behavioral components of play were equally diminished. In this study, the effects of amphetamine on both the attack and defense patterns of play fighting were analyzed. Experiment 1 shows that a 0.5 mg/kg dose, injected subcutaneously in the nape, decreases both attack and defense. In contrast, Experiment 2 shows that the same dose, injected subcutaneously in the hip, decreases the level of attack to a similar level, but does not significantly affect defense. This suggests that while the 0.5 mg/kg dose of amphetamine is primarily affecting the attack components of play, via its action on the central nervous systems, the reduced likelihood of defense for those rats injected in the nape probably results from a local anesthetic effect, which numbs the area of the body defended during play fighting. Further doses (0.15 & 1.0 mg/kg), injected in the hip, were also tested. The highest dose decreased both components of play. The lowest dose had no effect on either attack or defense. It is suggested that the attack and defensive components of play fighting may be mediated by different neural systems.