Effects of a Single Administration of Oxytocin or Vasopressin and Their Interactions with Two Selective Receptor Antagonists on Memory Storage in Mice

• Published in: Neurobiology of learning and memory 1998-03, Vol.69 (2), p.136-146
• Main Authors: Boccia, M.M., Kopf, S.R., Baratti, C.M.
• Format: Article
• Language: English
• Subjects: Animals; Antidiuretic Hormone Receptor Antagonists; Avoidance Learning - drug effects; Behavior, Animal - drug effects; Behavioral psychophysiology; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; inhibitory avoidance; Male; Memory - drug effects; memory storage; Mice; Neurotransmission and behavior; oxytocin; Oxytocin - pharmacology; oxytocin receptor antagonists; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Receptors, Oxytocin - antagonists & inhibitors; Receptors, Oxytocin - drug effects; Receptors, Vasopressin - drug effects; Vasoconstrictor Agents - pharmacology; vasopressin; vasopressin receptor antagonists; Vasopressins - pharmacology
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1006/nlme.1997.3817

The neuropeptides arginine vasopressin (AVP) and oxytocin (OT) have been thought to play a significant role in behavioral regulation in general and in learning and memory in particular. Experimental evidence suggests that AVP improves, and OT impairs, learning and memory. The present paper investigates the posttraining effects of OT and of an OT receptor antagonist, and their interaction, on memory storage in mice. Additional studies were conducted to determine the specificity of the interaction between OT and its receptors. Male Swiss mice were tested 48 h after training in a one-trial step-through inhibitory avoidance task. Immediate posttraining subcutaneous injection of OT (0.01, 0.03, 0.10, 0.30, and 1.00 μg/kg) impaired retention performance. The dose–response curve showed a U-shaped form, with a significant impairment seen at doses of 0.10 and 0.30 μg/kg of OT. In contrast, the immediate posttraining administration of the putative oxytocin receptor antagonistd(CH2)5[Tyr(Me)2, Thr4, Thy-NH92]OVT (AOT, 0.03, 0.10, 0.30, and 1.00 μg/kg) significantly enhanced retention performance. The dose–response curve was an inverted “U” in this range of doses. However, of the doses tested, only 0.30 μg/kg was effective. Neither OT nor AOT affected response latencies in mice not given the footshock on the training trial, indicating that the actions of both treatments on retention performance were not due to nonspecific proactive effects on response latencies. Neither the imparing effects of OT (0.10 μg/kg) nor the enhancing effects of AOT (0.30 μg/kg) were seen when the training–treatment interval was 180 min, suggesting that both treatments influenced the storage of recently acquired information. The effects of OT (0.10 μg/kg) on retention were prevented by AOT (0.03 μg/kg) administered immediately after training, but 10 min prior to oxytocin treatment. This dose of antagonist did not affect retention by itself, either under the standard experimental conditions or in mice trained with a lower level of footshock. On the contrary, OT (0.10 μg/kg) impaired retention in mice pretreated with the V1avasopressin receptor antagonistd(CH2)5[Tyr(Me)2]AVP (0.01 μg/kg), which, however, was able to prevent the enhancement of retention induced by posttraining administration of AVP (0.03 μg/kg). Finally, the effects of AVP (0.03 μg/kg) on retention were not prevented by AOT (0.03 μg/kg). Considered together, these findings suggest that the impairment of retention of an inhibitor