Neurochemical evidence for differential effects of acute and repeated oxytocin administration

Neurochemical effects of oxytocin in people at clinical high risk for psychosis

“…Choline levels in the ACC also appeared to be decreased by oxytocin, albeit at a relaxed significance threshold (p=.02, uncorrected for multiple comparisons; see supplementary material in (Aoki et al, 2015)). In a separate randomised, double-blind, placebo-controlled, crossover trial of 48IU/day oxytocin, which was administered repeatedly over 6 weeks in people with autism spectrum disorder, oxytocin significantly reduced levels of Glx and N-acetylaspartate in the medial prefrontal cortex/ACC relative to placebo (Benner et al, 2018). This prior work demonstrates that exogenously administered oxytocin can alter levels of metabolites as measured by 1H-MRS.…”

“…Third, the observed lack of effects (especially on glutamate and Glx) may be related to the acute vs long-term effects of repeated oxytocin administration. A recent study found that repeated administration of 48IU/day intranasal oxytocin over 6 weeks in people with autism spectrum disorder significantly decreased N-acetylaspartate and Glx levels in the medial prefrontal cortex (Benner et al, 2018), effects that were not observed after 24IU acute challenge (Aoki et al, 2015). Akin to the current work, both of the aforementioned studies were randomised, double-blind, placebo-controlled, crossover designs (Aoki et al, 2015;Benner et al, 2018).…”

“…A recent study found that repeated administration of 48IU/day intranasal oxytocin over 6 weeks in people with autism spectrum disorder significantly decreased N-acetylaspartate and Glx levels in the medial prefrontal cortex (Benner et al, 2018), effects that were not observed after 24IU acute challenge (Aoki et al, 2015). Akin to the current work, both of the aforementioned studies were randomised, double-blind, placebo-controlled, crossover designs (Aoki et al, 2015;Benner et al, 2018). In addition, their mouse model showed that repeated-but not acuteoxytocin administration significantly downregulated Nr2b (a subunit of the glutamate NMDA receptor) transcript expression, while acute administration reduced levels of molecules associated with the oxytocinergic system (oxytocin mRNA) and with neural activity (immediate early genes; cFos and Arc), but not Nr2b (Benner et al, 2018).…”

“…Akin to the current work, both of the aforementioned studies were randomised, double-blind, placebo-controlled, crossover designs (Aoki et al, 2015;Benner et al, 2018). In addition, their mouse model showed that repeated-but not acuteoxytocin administration significantly downregulated Nr2b (a subunit of the glutamate NMDA receptor) transcript expression, while acute administration reduced levels of molecules associated with the oxytocinergic system (oxytocin mRNA) and with neural activity (immediate early genes; cFos and Arc), but not Nr2b (Benner et al, 2018). In light of these findings, it is possible that longer-term treatment with oxytocin would have had significant effects on the glutamate system, with altered metabolite levels detectable using 1 H-MRS.…”

“…In line with previous findings in CHR-P individuals, our primary aim was to assess the effects of oxytocin on levels of glutamate, and glutamate plus glutamine (Glx), in the left hippocampus, ACC and left thalamus (Bloemen et al, 2011;Shakory et al, 2018;Tibbo et al, 2004). In view of recent literature suggesting that N-acetylaspartate, myo-inositol and choline may be altered in populations at risk of psychosis (Bossong et al, 2018;Tandon et al, 2013), and that oxytocin's effects may involve several neurochemical pathways (Aoki et al, 2015;Benner et al, 2018;Ninan, 2011;Qi et al, 2012), our secondary aim was to examine the effects of oxytocin on these metabolite levels.…”