Oxytocin-dependent reopening of a social reward learning critical period with MDMA

Psychedelics reopen a critical period to induce metaplasticity, which dynamically regulates the potential for synaptic plasticity.

“Recent studies have shown that psychedelics reopen a critical period to induce metaplasticity, which dynamically regulates the potential for synaptic plasticity (46, 47).”

This critical window can be reopened in adult mice by administering MDMA in the presence of another mouse.

“Nardou et al. (50) also demonstrated that this critical window can be reopened in adult mice by administering MDMA in the presence of another mouse.”

Increased sensitivity to social reinforcement extended for at least 2 weeks post-administration in mice.

“Furthermore, this increased sensitivity to social reinforcement extended for at least 2 weeks post-administration.”

MDMA needed to be administered with another mouse present in order to achieve this enduring shift in social reinforcement, suggesting that the social context of MDMA administration is important.

“Additionally, they also established that the MDMA needed to be administered with another mouse present in order to achieve this enduring shift in social reinforcement, suggesting that the social context of MDMA administration is important.”

Mice exhibit a critical period through adolescence when they find social encounters with stranger mice reinforcing but then lose this preference as they age.

“In a series of experimental studies, Nardou et al. (50) showed that mice exhibit a critical period through adolescence when they find social encounters with stranger mice reinforcing but then lose this preference as they age.”

There is a critical developmental window during adolescence when mice can optimally learn social rewarding cues and thereby exhibit social conditioned place preference.

“It has also been reported that there is a critical developmental window during adolescence when mice can optimally learn social rewarding cues and thereby exhibit social CPP [42].”

Paraventricular oxytocin cells are responsible for the facilitatory effects of MDMA on mouse prosocial behavior and social reward memory.

“Further, PVN OXT cells are responsible for the facilitatory effects of 3,4-methylendioxymethamphetamine (MDMA) on mouse prosocial behavior and social reward memory (81).”

Changes in locomotor activity are unlikely to account for differences in sCPP across a variety of experimental manipulations.

“Previously, we have shown that changes in locomotor activity are unlikely to account for differences in sCPP across a variety of experimental manipulations (Dölen et al., 2013; Nardou et al., 2019)”

Animal studies indicate that oxytocin plays an important role in MDMA-related social effects.

“This is in contrast to animal studies indicating that oxytocin plays an important role in MDMA-related social effects (103, 104).”

MDMA has been shown to enhance fear memory extinction, modulate fear memory reconsolidation, and bolster social behavior in animal models.

“MDMA has been shown to enhance fear memory extinction, modulate fear memory reconsolidation (possibly through an oxytocin-dependent mechanism), and bolster social behavior in animal models13,14.”

Given the subjective effects of MDMA, the blinding of participants was challenging and possibly led to expectation effects.

“Last, given the subjective effects of MDMA, the blinding of participants was also challenging and possibly led to expectation effects14.”