Effects of oxytocin administration and conditioned oxytocin on brain activity: An fMRI study.

Aleksandrina Skvortsova,Henriët Van Middendorp,Marinus Van Ijzendoorn,Marian Bakermans-Kranenburg,Gustavo Pacheco-Lopez,Mischa De Rover,Niels H Chavannes,Dieuwke S Veldhuijzen,Andrea W M Evers

doi:10.1371/journal.pone.0229692

Abstract

It has been demonstrated that secretion of several hormones can be classically conditioned, however, the underlying brain responses of such conditioning have never been investigated before. In this study we aimed to investigate how oxytocin administration and classically conditioned oxytocin influence brain responses. In total, 88 females were allocated to one of three groups: oxytocin administration, conditioned oxytocin, or placebo, and underwent an experiment consisting of three acquisition and three evocation days. Participants in the conditioned group received 24 IU of oxytocin together with a conditioned stimulus (CS) during three acquisition days and placebo with the CS on three evocation days. The oxytocin administration group received 24 IU of oxytocin and the placebo group received placebo during all days. On the last evocation day, fMRI scanning was performed for all participants during three tasks previously shown to be affected by oxytocin: presentation of emotional faces, crying baby sounds and heat pain. Region of interest analysis revealed that there was significantly lower activation in the right amygdala and in two clusters in the left superior temporal gyrus in the oxytocin administration group compared to the placebo group in response to observing fearful faces. The activation in the conditioned oxytocin group was in between the other two groups for these clusters but did not significantly differ from either group. No group differences were found in the other tasks. Preliminary evidence was found for brain activation of a conditioned oxytocin response; however, despite this trend in the expected direction, the conditioned group did not significantly differ from other groups. Future research should, therefore, investigate the optimal timing of conditioned endocrine responses and study whether the findings generalize to other hormones as well.

Highlights

It has been shown that after repeated administration of medication that triggers a physiological change, with an initially neutral conditioned stimulus (CS; such as, a taste or smell of the medication or the medication administration procedure), the CS alone can cause this physiological change [1]
Oxytocin has been shown to reduce amygdala activation in response to aversive [14] and painful stimuli [20], which can be an underlying mechanism of stress reducing [21] and analgesic [22] effects of oxytocin described in previous research. Considering these positive physiological and psychological effects of oxytocin, pharmacological conditioning of oxytocin might have important clinical implications both in somatic and mental health. In this randomized placebo-controlled trial, we investigated the effects of oxytocin administration and conditioned oxytocin in comparison to a placebo-control group on brain activation in response to fMRI tasks that have previously shown to be affected by exogenous oxytocin administration: presentation of emotional faces [12], presentation of crying baby sounds [23] and thermal pain stimulation [18, 20]
We hypothesized that conditioned oxytocin responses would demonstrate patterns of brain activation similar to exogenous oxytocin administration and that both these groups would differ from the placebo group

Summary

Introduction

It has been shown that after repeated administration of medication that triggers a physiological change (unconditioned response), with an initially neutral conditioned stimulus (CS; such as, a taste or smell of the medication or the medication administration procedure), the CS alone can cause this physiological change [1]. This principle is known as pharmacological conditioning. Evidence of the effects of pharmacological conditioning exists for other hormones, such as growth hormone [4] and insulin [5], and for immune parameters, such as interleukin-2 [6], natural cell killer activity [7] and histamine [8]

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