Leslie R. Meek

Effects of stress during pregnancy on maternal behavior in mice

The effects of stress experienced during pregnancy and raising stressed offspring on maternal behavior were investigated in Swiss-Webster mice. Dams were either stressed or not stressed during pregnancy, and raised either prenatally stressed or nonstressed cross-fostered pups. Maternal behaviors such as grooming, nursing, pup retrieval and maternal aggression were assessed during the first 4 days after birth. Nonstressed dams raising stressed pups and stressed dams raising nonstressed pups groomed and nursed their pups significantly less than did control dams (stressed dams raising stressed pups and nonstressed dams raising nonstressed pups). Nonstressed dams raising stressed pups were also the slowest to retrieve both the first and last pup in retrieval tests. Nonstressed dams raising nonstressed pups were significantly less aggressive than other dams. In contrast, stressed dams raising stressed pups exhibited high levels of nursing and grooming, retrieved their pups rapidly and were very aggressive towards an intruder. These results indicate that raising stressed pups, or experiencing stress during a pregnancy can have significant effects on maternal behaviors. Stressed dams raising stressed pups exhibit maternal care comparable to that of nonstressed dams raising nonstressed pups at least for nesting/nurturing behaviors, and show increased levels of aggression and pup retrieval.

Effects of prenatal stress on development in mice: maturation and learning

Female CD-1 mice were stressed during the final week of gestation. Beginning 3 days after birth, until weaning, their pups were examined for eye opening, startle response, tooth eruption, surface righting, ability to cling to and climb an incline, tail pull reflex, rotation, linear movement and exploration. At 3 months of age, they were tested in a Morris Water Maze. Stressed animals were significantly lighter and shorter than non-stressed animals the first week after birth. By 3 days after birth, significantly fewer stressed animals could rotate or right themselves. By 6 days after birth, significantly fewer stressed animals could cling to or climb an inclined screen, or show the tail pull reflex. By 9 days of age, significantly fewer stressed animals had teeth. In contrast, by day 12 of age, significantly more stressed animals demonstrated exploratory behavior than did non-stressed animals. There were no sex differences in the ability of animals to perform these tasks at the same age. Stressed animals were significantly slower than non-stressed animals to reach the hidden platform in the water maze on all trials, and this difference was due to stressed females being slower to find the platform than non-stressed females, with no main effect of stress on males. This study supports and expands previous findings in rodents that prenatal stress can cause deficiencies in some early indices of physical maturation and also that these deficiencies can be continued into adulthood.

Sexual and Reproductive Behaviors

The procedures described in this unit include testing procedures for male and female reproductive behaviors, gonadectomy, and hormonal treatments appropriate for inducing male and female reproductive behaviors. Because reproductive behaviors are social behaviors, and therefore require the presence of stimulus animals, the protocols in this unit also provide information on the preparation of stimulus animals. The protocols are written for use with laboratory rats, although a discussion of issues related to species differences in the study of reproductive behaviors is included.

Acute paternal alcohol use affects offspring development and adult behavior

Swiss Webster pups were fathered by sires given either an acute dose of alcohol (alcohol-sired) or saline (saline-sired) 12-24 h before mating. The same sires were used to father both groups of pups. Alcohol-sired pups were significantly lighter at birth and for the following three weeks than were saline-sired pups. Significantly more pups were fathered by saline-exposed sires, and dams carrying those pups had significantly longer gestations than those carrying pups of alcohol-using sires. More runts were born to the alcohol-sired group, and more pups in that group died over the next three weeks than in the saline-sired group. Significantly more pups in the saline-sired group achieved such developmental milestones as surface righting, clinging, the tail-pull reflex, rotation, linear movement and climbing an inclined surface earlier than did alcohol-sired pups. As adults, animals from the alcohol-sired group showed significantly less risk assessment behavior and longer latencies to such behaviors as stretched attention, flatback, freezing and defensive burying than did the saline-sired animals. Alcohol-sired animals contacted the stimulus object in the risk assessment test significantly sooner and more often than did the saline-sired group. In tests of aggression, alcohol-sired male offspring showed more frequent aggressive behaviors such as on-top, lateral attacks and jump-attacks, and significantly fewer defensive/fearful behaviors such as piloerection, tail rattling and jump-escape. This pattern of results suggests that exposure of the sire to one acute dose of alcohol before insemination caused some early developmental delays and that alcohol-sired animals are less fearful and more aggressive as adults than saline-sired animals.

Effects of prenatal stress on sexual partner preference in mice.

Three-month old, male Swiss Webster mice were born to either control dams or dams who had been prenatally stressed with light, heat, noise and handling during the last week of gestation. As adults, male offspring were tested on sexual partner preference and sexual behavior (mounting, intromissions and lordosis) with a sexually experienced male stimulus animal and a stimulus estrous female. In comparison to males born to control dams, prenatally stressed males showed a sexual partner preference for the sexually active male as demonstrated by a negative partner preference score, more and longer visits to the males compartment, fewer and shorter visits to the females compartment and longer latencies to and lower frequencies of mounts and intromissions of females. In addition, stressed males showed a greater frequency of lordosis and a higher lordosis quotient than did control males. This study is the first to investigate the effects of prenatal stress alone, without hormonal manipulation, on sexual partner preference using both a partner preference paradigm and measures of sexual behavior such as mounting, intromissions and lordosis. These findings support the suggestion that prenatal stress alone is enough to significantly affect sexual partner preference in male mice.

Effects of Fluprazine Hydrochloride on Reactivity to a Nonconspecific Intruder

Treatment with 8.0 mg/kg of fluprazine hydrochloride completely suppressed defensive burying of albino mice directed toward an intruding tiger salamander. This treatment also increased mouse-salamander social distances. The results are consistent with earlier data in suggesting that fluprazine potentiates tearfulness and indicate that this effect extends to nonconspecific intruders as well as novel inanimate stimuli, shock, and conspecifics. This rather generalized drug-induced tearfulness may contribute heavily to fluprazine’s potent inhibition of offense, maternal behavior, play, and predation.

Effects of Fluprazine Hydrochloride on Three Aversively Motivated Tasks

Treatment with 8.0 mg/kg fluprazine hydrochloride had no effect on the acquisition of a step-down avoidance response but retarded its extinction. The drug also impaired acquisition of a jump-up active avoidance response if the rats received inescapable footshock 30 min prior to training, but had no effect if inescapable shock immediately preceded acquisition or was absent. In contrast, fluprazine treatment produced an immediate impairment on the acquisition of an escape response in a water maze. The results are consistent with earlier findings in suggesting that fluprazine produces a prolonged, and perhaps delayed, increase in responsiveness to shock. This pattern of reactivity may be restricted to painful stimuli. The combined effects of fluprazine on both painful and nonpainful sources of aversive stimuli may contribute to its disruption of aggression and other social behaviors in an important way.

Effects of dominance status on defensive burying in male mice

Two experiments with male mice explored the effects of intermale dominance status on defensive burying. In the first experiment, there was no relationship between readiness to enter a novel open field and conditioned defensive burying, but males showing extensive scarring near the base of the tail, associated with lower dominance status, defensively buried less than did their unscarred, and presumably more dominant, counterparts. In the second experiment, mice that were dominant in a food competition test showed significantly more unconditioned, but not conditioned, burying than did those that were subordinate. The results of these experiments suggest that prior intermale dominance interactions contribute to an animal’s propensity to defensively bury.

Effects of Eltoprazine Hydrochloride on Predatory Behavior in Rats

Treatment of rats with the potent antiaggressive compound eltoprazine hydrochloride (1.0 & 2.0 mg/kg) slowed both predatory attack and killing of frogs. These results demonstrate a specific predation-inhibiting action of the drug which is not obscured by the elements of conspecific aggression seen during muricide. Unlike the closely related compound fluprazine, eltoprazine increased both attack and kill latencies implying that the effects of the two drugs on predation are mediated by at least somewhat distinct drug actions. It is further suggested that eltoprazine may be more specifically antiaggressive in its actions than related phenylpiperazine compounds.

Female meadow voles housed in long and short daylengths respond to exogenous estrogen with similar mating latencies

After weaning, adult female meadow voles were maintained for 7 weeks in either long (LD, 14 h light/day) or short photoperiods (SD, 10 h light/day). They were then ovariectomized and implanted with 3-week, timed-release estrogen pellets (0.0, 0.001, 0.05, or 0.5 mg/pellet of 17-beta-estradiol). An additional group received a sham ovariectomy (intact) and a 0.0-mg/pellet control (no estrogen) pellet. One week after surgery, females were paired with an LD sexually experienced male. Each pair was videotaped continuously until the first intromission or for 2 weeks. LD sham animals mated significantly earlier than did SD sham animals (P=.05). However, there were no differences in mating latencies between LD and SD control groups or between any of the LD and SD groups receiving estrogen replacement (P>.05). In addition, no ovariectomized animals receiving either the control or the 0.001-mg/pellet estrogen dosage mated within the 2-week time period, while all shams and all animals receiving either the 0.05- or 0.5-mg/pellet doses mated. The results indicate that there is some minimal amount of estrogen that is necessary for meadow voles to enter behavioral estrus and that LD and SD females do not differ in their sensitivity to estrogen, since animals in both photoperiods mate with similar latencies as long as enough estrogen is present.