Projects PD Dr. Oliver Bosch
"MATERNAL BEHAVIOR GROUP"

I. Why is a lactating animal less anxious and more aggressive?

For the defense of their offspring, lactating rats display maternal aggression, which is part of the complex maternal behavior. The amount of aggression depends on the innnate level of anxiety; a highly anxious dam is more aggressive compared to a less anxious dam. We are especially interested in the neurobiological mechanisms underlying these behavioral adaptations in maternal aggression using female Sprague-Dawley as well as Wistar rats as an animal model. In addition, we use Wistar rats selectively bred for high (HAB) or low (LAB) anxiety-related behavior. With respect to the regulation of behavior, the neuropeptides oxytocin and vasopressin in mediating both anxiety-related behavior and aggression are in our focus.

Fig. 1 Elevated Plus-Maze

The rats are tested for anxiety-related behavior on the "Elevated Plus-Maze" (Fig. 1); their behaviors are quantified via a video-computer-setup.

Fig. 2 Maternal Defense

The quantity and quality of the aggressive behavior displayed by the lactating rat, e.g. the number of attacks against an intruder, is tested during the "maternal defense test" (Fig. 2). During this test, local release patterns of neuropeptides can be quantified in selected brain regions like the hypothalamic paraventricular nucleus or the limbic central amygdala using intracerebral microdialysis followed by radioimmunoassay. In addition, retrodialysis of selective receptor antagonists allows us to manipulate the local effects of oxytocin or vasopressin, e.g., on the behavior.

Using this technique we could demonstrate that besides its well-known reproductive effects (labour, milk ejection, maternal care; Fig. 3) oxytocin has also anxiolytic effects (decreases anxiety) and increases aggression in the female rat when released within hypothalamic and limbic brain regions. Furthermore, while vasopressin has anxiogenic properties, its local release within the central amygdala promotes maternal aggression.

Fig. 3 Maternal Care

In cooperation with: Prof. J. A. Russell / Dr. A. J. Douglas / Dr. S. Meddle, Centre for Neuroscience Research, University of Edinburgh (UK)


II. Does chronic pregnancy stress alter maternal behavior and stress coping post partum?

So far, chronic effects of stress during pregnancy on the behavior are mainly described in offspring (s. below). However, it is less known how chronic pregnancy stress affects the emotionality and neuroendocrine parameters of the dam. In context with the development of post partum depression, which is a serious risk factor in women after parturition, pregnant rats are exposed to a ethiological-relevant psycho-social stressor. We found that the primary adaptation of the endocrine stress response in undisturbed lactating rats (Fig. 4) is impaired after pregnancy stress. Using our breeding lines of rats with high (HAB) and low (LAB) anxiety-related behavior we are able to focus on how pregnancy stress affects their genetic predisposition for anxiety.

Fig. 4 Adaptation of the endocrine stress response during lactation

III. Stress during pregnancy: Does it affect the emotional development of the offspring due to their genetic predisposition?

Repeated exposure of the pregnant rat to stress has severe consequences on the emotional, cognitive, and neuroendocrine development of the offspring, which has also been shown in humans. In adulthood, prenatally stressed individuals are, e.g., more anxious, have impairments in learning, show less social abilities, and have an unphysiologically high endocrine response to a mild stressor (Fig. 5).

Fig. 5 Elevated Platform

In this project, we are interested in the interaction of early environmental factors (prenatal stress) and genetic predisposition. Therefore, we are using rats from our own HAB and LAB lines as they are selected and bred for differences in anxiety. Our aim is to identify the neurobiological basis for differences in stress vulnerability early in life. Here, we quantify the expression (in-situ hybridization) or release (mikrodialysis) of vasopressin or CRH in the hypothalamus of these rats.

In cooperation with: Prof. R. Landgraf, Max-Planck-Institut for Psychiatry, Munich (GER)

Supported by the VolkswagenStiftung


IV. The use of adeno-viral vectors in behavioral neuroendocrinology


To test the involvement of neuropeptides in emotionality and the endocrine stress response selective receptor antagonists can be used to block the binding sites of the receptors for their neuropeptides. A further possibility to alter receptor binding capacities is the use of adeno-viral vectors for gene transfer. As a result, the expression and, thus, the amount and function of a special type of receptor can be increased. In cooperation with scientists from the Emory University of Atlanta, USA, adeno-viral vectors for, e.g., vasopressin receptors were developed, which can be locally injected in selected brain regions of the experimental animal. The resulting overexpression of the receptor should increase the possible action of the locally released neuropeptide, which then results in changes of the behavior or of endocrine parameters in response to stress exposure.

Fig. 6 Schematic construction of the vasopressin receptor plasmid via insertion of a modified vasopressin receptor clone (V1aR) between a neuron-specific promotor (NSE) and a polyA signal (pA)

The treated animals are examined in relevant behavioral test for emotionality and the plasma levels of their stress hormones ACTH and corticosterone are quantified. So far, we could show in a collaboration with scientists from the Max-Planck-Institute for Psychiatry, Munich, GER, that an overexpression of vasopressin in the septum results in improved social memory in male rats.

In cooperation with: Prof. L. Young & Dr. H. Nair, Yerkes Center, Emory University, Atlanta/GA (USA)


Supported by the DAAD/NSF