Neuropeptides vasopressin (AVP) and oxytocin (OXY) have not only typical physiological peripheral effects but they also have significant central regulatory actions as neuromodulators and neurotransmitters. Recent studies have shown that these neuropeptides modulate a variety of neurophysiological phenomena including behavior, learning, memory and they also modify stress responses. Very important are findings showing that OXY is responsible for some psychic disorders, and therefore new therapeutic approaches are searched among analogs of OXY. The aim of this study was investigation of the effect ofOXY receptor antagonists on spontaneous behavior of rats influenced by peripheral application of oxytocin or its long lasting analog carbetocin; for evaluation of spontaneous behavior of rats was selected open-field device. We used male Wistar rats that were injected i.p. by agonists and/or antagonists 60 min before the start of behavioral test in the open-field. Spontaneous behavior of rats (horizontal) was video-monitored by automated activity monitoring system (AnyMaze, Stoelting, USA) in a circular arena with diameter of 150 cm. Rearing and grooming (face washing, body and genital grooming, body and paw licking and scratching) were recorded by the experimenter. As OXY receptor antagonists we used a nonpeptide antagonist L-368,899 (Tocris, UK), as classical antagonist we applied clinically used atosiban (Polypeptide Labs, Sweden), and as highly selective OXY antagonist we synthesized cpmProp-D-Tyr-Ile-Thr-Asn-Cys-Pro-Orn-NH2, originally prepared by Manning et al. (1). We found that all three oxytocin antagonists (non-peptide as well as peptide) revealed very similar effects that are characterized by complete blocking of grooming while other behavioral parameters, like horizontal and vertical exploratory activities, were antagonized only partially. It is possible to consider that this diversity in their antagonistic actions on oxytocin induced behavioral parameters and grooming can be explained by differences in receptor localization and/or involvement of different signaling pathways.

Manning et al. Int. J. Pep. Protein Res. 46:244-252, 1995.

Acknowledgment: 

Supported by grant MSM 0021620806.