The Effects of Prenatal Exposure to Altered Melatonin Levels on Hippocampal Gene Expression in the Male Rat

The stability of the circadian rhythm for mammals depends on the levels of serotonin and melatonin, neurohormones that signal for lightness and darkness, respectively. Disruption in the stability of neurohormones has been shown to be a critical factor in psychopathological disorders in humans. For example, altering levels of melatonin in utero through administration of melatonin or the melatonin receptor antagonist, luzindole, has been shown to cause changes in developmental growth and adult behavior in the male rat. Analysis of relative adult hippocampal gene expression with RT-PCR revealed differences in ARNTL expression that suggested abnormality in clock gene expression of the rats that were prenatally exposed to altered levels of melatonin. Differences in the degree of plasticity as suggested by previous behavior testing did not result in differences in gene expression for GABA receptors or NMDA receptors. Morevoer, growth associated protein 43, GAP-43, a protein that is necessary for neuronal growth cones as well as long term learning has been found to be critical for axon and presynaptic terminal formation and retention in other studies, but hippocampal gene expression in our study showed no significant alteration after exposure to various maternal melatonin levels. However, ARNTL is a key regulatory component of clock genes and the circadian cycle so that alterations in the expression of thi critical gene may lead to critical changes in neuronal growth and plasticity. Our data support the conclusion that the manipulation of maternal melatonin levels alters the brain development and the circadian cycles that may lead to physiological and behavioral abnormalities in adult offspring.

The Effect of Chronic Estrogen Administration on Same-Sex Social Behavior and Central Oxytocin Levels in Prairie Voles (Microtus ochrogaster)

The purpose of our study is to investigate the effects of chronic estrogen administration on same-sex interactions during exposure to a social stressor and on oxytocin (OT) levels in prairie voles (Microtus orchrogaster). Estrogen and OT are two hormones known to be involved with social behavior and stress. Estogen is involved in the transcription of OT and its receptor. Because of this, it is generally thought that estrogen upregulates OT, but evidence to support this assumption is weak. While estrogen has been shown to either increase or decrease stress, OT has been shown to have stress-dampening properties. The goal of our experiment is to determine how estrogen affects OT levels as well as behavior in a social stressor in the voles. In addition, estrogen is required for many opposite-sex interactions, but little is known about its influence on same-sex interactions. We hypothesized that prairie voles receiving chronic estrogen injections would show an increase in OT levels in the brain and alter behavior in response to a social stressor called the resident-intruder test. To test this hypothesis, 73 female prairie voles were ovariectomized and then administered daily injections of estrogen (0.05 ¿g in peanut oil, s.c.) or vehicle for 8 days. On the final day of injections, half of the voles were given the resident-intruder test, a stressful 5 min interaction with a same-sex stranger. Their behavior was video-recorded. These animals were then sacrificed either 10 minutes or 60 minutes after the conclusion of the test. Half of the animals (no stress group) were not given the resident-intruder test. After sacrifice, trunk blood and brains were collected from the animals. Videos of the resident-intruder tests were analyzed for pro-social and aggressive behavior. Density of OT-activated neurons in the brain was measured via pixel count using immunohistochemistry. No differences were found in pro-social behavior (focal sniffing, p = 0.242; focal initiated sniffing p = 0.142; focal initiated sniffing/focal sniffing, p = 0.884) or aggressive behavior (total time fighting, p= 0.763; number of fights, p= 0.148; number of strikes, p = 0.714). No differences were found in activation of OT neurons in the brain, neither in the anterior paraventricular nucleus (PVN) (pixel count p= 0.358; % area that contains pixelated neurons p = 0.443) nor in the medial PVN (pixel count p= 0.999; % area that contains pixelated neurons p = 0.916). These results suggest that estrogen most likely does not directly upregulate OT and that estrogen does not alter behavior in stressful social interactions with a same-sex stranger. Estrogen may prepare the animal to respond to OT, instead of increasing the production of the peptide itself, suggesting that we need to shift the framework in which we consider estrogen and OT interactions.