Deficits in male sexual behavior in adulthood after social instability stress in adolescence in rats.

There is increasing evidence that exposure to stressors in adolescence has long-lasting effects on emotional and cognitive behavior, but little is known as to whether reproductive functions are affected. We investigated appetitive and consummatory aspects of sexual behavior in male rats that were exposed to chronic social instability stress (SS, n=24) for 16 days in mid-adolescence compared to control rats (CTL, n=24). Over five sexual behavior test sessions with a receptive female, SS rats made fewer ejaculations (p=0.02) and had longer latencies to ejaculation (p=0.03). When only data from rats that ejaculated in the fifth session were analyzed, SS rats (n=18) had reduced copulatory efficiency (more mounts and intromissions before ejaculation) compared to CTL rats (n=19) (p=0.004), and CTL rats were twice as likely as SS rats to make more than one ejaculation in the fifth session (p=0.05). Further, more CTL (14/24) than SS (5/25) rats ejaculated in four or more sessions (p=0.05). SS rats had lower plasma testosterone concentrations than CTL rats (p=0.05), but did not differ in androgen receptor, estrogen receptor alpha, or Fos immunoreactive cell counts in the medial preoptic area. The groups did not differ in a partner preference test administered between the fourth and fifth sexual behavior session. The results suggest that developmental history contributes to individual differences in reproductive behavior, and that stress exposures in adolescence may be a factor in sexual sluggishness.

Social instability stress in adolescent male rats alters hippocampal neurogenesis and produces deficits in spatial location memory in adulthood.

The ongoing development of the hippocampus in adolescence may be vulnerable to stressors. The effects of social instability stress (SS) in adolescence (daily 1 h isolation and change of cage partner postnatal days 30-45) on cell proliferation in the dentate gyrus (DG) in adolescence (on days 33 and 46, experiment 1) and in adulthood (experiment 2) was examined in Long Evans male rats and compared to nonstressed controls (CTL). Additionally, in experiment 2, a separate group of SS and CTL rats was tested on either a spatial (hippocampal-dependent) or nonspatial (nonhippocampal dependent) version of an object memory test and also were used to investigate hippocampal expression of markers of synaptic plasticity. No memory impairment was evident until the SS rats were adults, and the impairment was only on the spatial test. SS rats initially (postnatal day 33) had increased cell proliferation based on counts of Ki67 immunoreactive (ir) cells and greater survival of immature neurons based on counts of doublecortin ir cells on day 46 and in adulthood, irrespective of behavioral testing. Counts of microglia in the DG did not differ by stress group, but behavioral testing was associated with reduced microglia counts compared to nontested rats. As adults, SS and CTL rats did not differ in hippocampal expression of synaptophysin, but compared to CTL rats, SS rats had higher expression of basal calcium/calmodulin-dependent kinase II (CamKII), and lower expression of the phosphorylated CamKII subunit threonine 286, signaling molecules related to synaptic plasticity. The results are contrasted with those from previous reports of chronic stress in adult rats, and we conclude that adolescent stress alters the ongoing development of the hippocampus leading to impaired spatial memory in adulthood, highlighting the heightened vulnerability to stressors in adolescence.

Hippocampal cell proliferation and spatial memory performance after social instability stress in adolescence in female rats.

We investigated the immediate and lasting effect of social instability stress in adolescence [SS: daily 1h isolation and change of cage partner postnatal days (P) 30-45] on cell proliferation in the hippocampus and on spatial memory using an object spatial location (SL) test. Female rats were treated with bromodeoxyuridine (BrdU) P43-45, and on P49, SS had reduced cell hippocampal cell proliferation/survival compared to controls as indicated by BrdU immunoreactive cell counts (p=0.009), and did not differ in Ki67 immunoreactive cell counts (p=0.15) from CTL. A separate group of SS and CTL rats were tested at P47 and P48, and again at P72 and P73 on the SL test using 1 and 8h retention intervals. SS and CTL females did not differ in adolescence, but CTL had better memory than SS as adults (p=0.03). The better memory performance of CTL rats is not due to differential investigation of objects during the familiarization pre-tests or by differential locomotor activity. The lasting memory reduction and reduced cell proliferation/survival in SS rats is consistent with the hypothesis that ongoing development of the hippocampus renders the adolescent particularly vulnerable to chronic social stress.