Oxytocin and carbetocin effects on spontaneous behavior of male rats: modulation by oxytocin receptor antagonists.
OBJECTIVE
Oxytocin (OXY) in addition to peripheral actions has many central regulatory functions which can be studied on animal models. In the present study we examined in rats, which behavioral actions of OXY and long-acting carba-analog of OXY carbetocin (CBT) in the open-field can be inhibited by OXY-receptor antagonists. Our interest focused on the behavioral patterns considered indicative of anxiety-related behavior. To determine what is the participation of OXY receptor on OXY and CBT induced behavioral changes, we used two peptide and one nonpeptide OXY antagonists differing in selectivity for OXY receptor.


METHODS
OXY, CBT as well as OXY antagonists were injected intraperitoneally, and spontaneous behavior (horizontal and vertical activity, grooming) of Wistar rats was observed in the circular open-field arena 60 min after application of drugs; in some experiments testing was performed without treatment few days after drug administration.


RESULTS
OXY at the dose 0.05 mg/kg increased locomotion indicating anxiety attenuation, but 1.0 mg/kg reduced both locomotion and rearing. CBT in the dose range 0.1-3.0 mg/kg either did not change or increased horizontal activity. The increase in exploration after both peptides persisted for several days. A marked difference in the behavioral effects of the two peptides was grooming enhancement induced by OXY compared with the absence of this effect after CBT. The increase of the activity induced by OXY and CBT indicating anxiolytic-like action was blocked by OXY antagonists. However, the reduction of exploration induced by 1.0 mg dose of OXY was only partially reversed. The OXY induced enhanced grooming was completely antagonized by all used antagonists.


CONCLUSIONS
Behavioral effects of OXY and its antagonists after their i.p. application indicate that they penetrate blood brain barrier. The diversity in potency of OXY antagonists to inhibit grooming and other behaviors induced by OXY suggests that receptors participating in these behaviors may differ in brain localization, receptor conformation and/or in the utilized signaling pathways.
Laboratory of Biochemical Neuropharmacology, Institute of Medical Biochemistry, 1st Faculty of Medicine, Charles University in Prague, Czech Republic. vera.klenerova@LF1.cuni.cz
Vera
V
Klenerova
Ivan
I
Krejci
Pavel
P
Sida
Zdenek
Z
Hlinak
Sixtus
S
Hynie
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001892:Camphanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006120:Grooming / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010120:Oxytocics / Q000008:administration & dosage; D010121:Oxytocin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000187:drug effects; D013315:Stress, Psychological / Q000188:drug therapy; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology
D001892:Camphanes; D006727:Hormone Antagonists; D010120:Oxytocics; D010879:Piperazines; D018045:Receptors, Oxytocin; C047046:atosiban; D010121:Oxytocin; C020731:carbetocin; C086206:L 368899; D014668:Vasotocin