Ž . Journal of the Autonomic Nervous System 78 1999 49–56 www.elsevier.comrlocaterjans Oxytocin enhances the effects of clonidine on blood pressure and locomotor activity in rats Maria Petersson a,b, ) , Thomas Lundeberg b , Kerstin Uvnas-Moberg b,c ¨ a Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden b Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden c Department of Animal Physiology, Swedish UniÕersity of Agricultural Sciences, Uppsala, Sweden Received 10 February 1999; received in revised form 12 August 1999; accepted 12 August 1999 Abstract Oxytocin treatment decreases blood pressure and changes the pattern of spontaneous motor activity. The aim of this study was to explore if alpha 2-adrenoreceptors that are involved in the regulation of blood pressure and spontaneous motor activity are influenced by Ž Ž .. oxytocin treatment. For this purpose, male rats were pretreated with oxytocin 1 mgrkg subcutaneously s.c. or saline once a day during Ž . Ž Ž . 5 days. Clonidine alpha 2-adrenoreceptor agonist decreased blood pressure 2.5 mgrkg intracerebroventricularly i.c.v. and 100 mgrkg . Ž . s.c. and changed spontaneous motor activity 100 mgrkg s.c. , observed in an open field arena, significantly more in oxytocin pretreated Ž . Ž .Ž . rats compared to saline pretreated controls P -0.05 . In contrast, idazoxan alpha 2-adrenoreceptor antagonist 50 mgrkg i.c.v. caused Ž . a significantly smaller elevation of blood pressure in the oxytocin pretreated rats P -0.05 . In addition, the effect on blood pressure of an alpha 1-adrenoreceptor agonist, phenylephrine, was evaluated. It increased blood pressure equally in the oxytocin- and saline pretreated rats. The present study shows that subchronic oxytocin treatment increases the effects of clonidine on blood pressure and spontaneous motor activity in rats. These findings imply that alpha 2-adrenoreceptors are involved in the effects of oxytocin treatment on blood pressure and spontaneous motor activity. q 1999 Published by Elsevier Science B.V. All rights reserved. Keywords: Oxytocin; Blood pressure; Locomotor activity; Alpha 2-adrenoreceptor; Idazoxan; Clonidine; Phenylephrine 1. Introduction The hypothalamic nonapeptide oxytocin may influence Ž both blood pressure and behavior for a review see Richard . et al., 1991 . If oxytocin is given repeatedly to rats, several of its effects are long-lasting. A 5 day treatment period Ž . with oxytocin 1 mgrkg intracerebroventricularly i.c.v. or Ž . 1 mgrkg subcutaneously s.c. decreases blood pressure Ž significantly in both male and female rats Petersson et al., . 1996a . Furthermore, a 5-day treatment period of oxytocin Ž . increases nociceptive thresholds Petersson et al., 1996b , changes the plasma levels of some vagally controlled Ž . hormones Petersson et al., 1999a as well as the pattern of Ž spontaneous motor activity Petersson and Uvnas-Moberg, ¨ . to be published and decreases corticosterone levels ) Corresponding author. Department of Physiology and Pharmacology, Karolinska Institutet, S-17177, Stockholm, Sweden. Tel.: q46-8-728- 7914; fax: q46-8-332-237; e-mail: maria.petersson@fyfa.ki.se Ž . Petersson et al., 1999b . Interestingly, all these antistress effects are sustained for more than a week after the end of the oxytocin treatment. We have recently found that repeatedly given oxytocin increases the responsiveness of alpha 2-adrenoreceptors Ž . within the noradrenergic nucleus locus coeruleus LC Ž . Petersson et al., 1998 . This nucleus is of central impor- tance for the stress response and it also takes part in the Ž regulation of blood pressure Van Bockstaele and Aston- . Jones, 1995 . Parvocellular oxytocinergic neurons from the Ž . paraventricular nucleus PVN project to many areas, in- cluding the LC, which are of importance for central cardio- vascular regulation, as well as for behavioral reactions. For example hippocampus, amygdala, striatum, the rostral ven- Ž . tral lateral part of the medulla RVLM , the vagal nuclei and the preganglionic sympathetic neurons are all reached Ž . by oxytocinergic neurons Buijs, 1983; Sofroniew, 1983 , indicating that oxytocin may influence the activity in these areas. Several of these areas are also richely provided with Ž . alpha 2-adrenoreceptors Nicholas et al., 1996 . 0165-1838r99r$ - see front matter q 1999 Published by Elsevier Science B.V. All rights reserved. Ž . PII: S0165-1838 99 00061-2