Research reportA single social defeat experience selectively stimulates the release of oxytocin, but not vasopressin, within the septal brain area of male rats
Introduction
The two nonapeptides oxytocin (OXT) and arginine vasopressin (AVP) are primarily synthesized in magnocellular neurons of the hypothalamic supraoptic (SON) and paraventricular nuclei (PVN). Both OXT and AVP are released from the hypothalamic-neurohypophysial system into the blood in response to appropriate stimulation (for review see [9]). In addition to this classical hypothalamic-pituitary pathway, cell bodies and fibers containing OXT and AVP are also found in various extrahypothalamic brain areas [5], [6], [39]. For example, fibers originating from the bed nucleus of the stria terminalis and the amygdala innervate limbic brain areas, such as the septum and hippocampus [7], [11], [12]. These observations imply that OXT and AVP act not only as hormones in the blood, but also as neuromodulators/neurotransmitters within distinct mammalian brain areas. Indeed, OXT and AVP seem to be critically involved in a variety of brain functions, such as the generation of emotions and learning and memory (for review see [15], [25]). Studies focusing on the intracerebral release of the two nonapeptides could demonstrate changes in the concentrations of OXT and AVP in the extracellular fluid of hypothalamic and limbic brain areas in response to a variety of stressful stimuli [13], [32], [44]. Recently, it could be shown that social defeat, associated with emotional stress, caused an increased release of OXT within the SON [16] and of AVP within the PVN [44].
Investigations on the site of action of intracerebrally released OXT and AVP on emotionality to cope with stress indicate that midbrain-limbic structures, like septum and amygdala, are critically involved in the behavioral response to emotionally challenging situations [20]. Binding studies confirmed existence of specific receptors for OXT and AVP within the septum [3], [33], [35], [38], [40]. In a recent study, we could demonstrate that stress-induced AVP release within the septum modulates the behavioral stress response of male rats in a forced swimming task driving animals to a more active coping strategy [13]. Furthermore, the reduction of effective binding sites for AVP within the septum by administration of either an AVP receptor antagonist [27] or antisense oligodeoxynucleotides targeting the mRNA of the V1 receptor subtype [23] altered the anxiety-related behavior of the animals.
On the basis of these observations, the present experiments were designed to investigate whether the exposure of an animal to an emotionally challenging situation, like social defeat, influences the release of OXT and/or AVP in the mediolateral septum. In the first experiment we monitored the release of OXT and AVP within the mediolateral septum under basal conditions and in response to social defeat using the microdialysis technique. In a second experiment we attempted to investigate the physiological significance of the observed increased release of OXT by analyzing behavioral parameters after local administration of an OXT receptor antagonist via inverse microdialysis.
Section snippets
Animals
Adult male Wistar rats (Charles River, Sulzfeld, Germany), weighting 300–400 g, were used in this study. Before surgery, animals were housed in groups of 4–6 for at least 1 week after delivery from the supplier. After surgery, rats were kept individually in transparent polycarbon cages (20×28×35 cm) under controlled standard laboratory conditions (23±2°C, 60±5% humidity, 12 h light/12 h dark cycle with lights on at 7:00 h) with free access to food and water.
Surgery
All surgical, sampling and behavioral
Experiment 1: Effects of emotional stress on the release of OXT and AVP within the septum during social defeat
As shown in Fig. 2A, social defeat caused a significant increase in the release of OXT within the mediolateral septum (F5,40=9.99; P<0.001), returning to pre-stress values within the next 60 min. In contrast, the release of AVP gradually decreased with increasing time (F5,35=2.56; P<0.044; Fig. 2B). AVP content of microdialysates collected from the lateral ventricle remained unchanged throughout the experiment (data not shown). OXT content of the same samples obtained from the ventricle was
Discussion
The aim of the present study was to investigate whether (1) an ethologically relevant stressful stimulus alters the release of the nonapeptides AVP and/or OXT within a limbic brain area and (2) the measured alterations are of behavioral relevance. We demonstrated that social defeat is a potent and selective stimulus to trigger the release of OXT, but not AVP, into the extracellular compartment of the mediolateral septum. The functional role of intraseptally released OXT, however, remains
Acknowledgements
The authors thank T.F.W. Horn for critical reading of the manuscript.
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