Key result
PVN oxytocin receptor blockade attenuates stress-evoked tachycardia, sympathetic tone, and delayed anxiety.
Why the study?
While oxytocin neurons in the paraventricular nucleus are known to be activated by restraint stress, the precise role of oxytocin in modulating psychological and cardiovascular stress responses was not fully understood.
Does bilateral intra-PVN administration of the oxytocin receptor antagonist L-368,899 modulate cardiovascular autonomic responses, corticosterone levels, and late anxiety-like behaviors in male Sprague Dawley rats subjected to acute restraint stress?
Does bilateral intra-PVN administration of the oxytocin receptor antagonist L-368,899 modulate cardiovascular autonomic responses, corticosterone levels, and late anxiety-like behaviors in male Sprague Dawley rats subjected to acute restraint stress?
In a rat model of acute restraint stress, blocking oxytocin receptors in the paraventricular nucleus alters cardiac autonomic balance by reducing sympathetic activity and increasing parasympathetic drive to attenuate stress-induced tachycardia, while high-dose blockade prevents late anxiety-like behavior without affecting corticosterone release.
PVN oxytocin receptors may mediate rodent stress autonomic responses; leaves open human translation or therapeutic targeting.
Stressful events are commonly linked to psychological and cardiovascular disorders. Restraint stress is a well-established model for studying these changes. While oxytocin (OXT) neurons in the paraventricular nucleus (PVN) are known to be activated by restraint stress, the precise role of OXT in this process is not fully understood. To investigate this, rats were subjected to one or two hours of restraint stress after receiving an OXT receptor antagonist (L-368,899) directly into the PVN (3, 6, or 9 nmol). During the stress, cardiovascular parameters such as mean arterial pressure (MAP) and heart rate (HR) were monitored, and their corticosterone levels were measured. 24 hours later, the animals underwent behavioral tests for anxiety (open field, elevated plus maze, and light/dark box). Restraint stress increased both MAP and HR. The OXT antagonist had complex effects on MAP, reducing it at the 3 nmol dose and increasing it at the 6 nmol dose. The antagonist also reduced the stress-induced heart rate increase at the 3 and 9 nmol doses. Heart rate variability analysis showed that the drug reduced sympathetic activity and increased parasympathetic activity, intensifying bradycardia. In behavioral tests, the antagonist increased anxiety-like responses, except for the 9 nmol dose, which prevented these responses. Corticosterone levels were elevated in all stressed animals, regardless of treatment. These findings suggest that OXT in the PVN plays a crucial role in modulating cardiovascular and behavioral responses to stress. Blocking its receptors altered sympathetic/parasympathetic cardiac regulation and reduced anxiety but did not affect the corticosterone axis.
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Belém-Filho et al. (2026) studied Acute restraint stress in male Sprague Dawley rats (n=71). Intra-PVN oxytocin receptor antagonist (L-368,899) vs. Vehicle (100 nL artificial cerebrospinal fluid / saline solution) and naive non-stressed controls was evaluated on Restraint stress-evoked cardiovascular responses (mean arterial pressure and heart rate) and anxiety-like behavior at 24 hours (p=<0.05). Intra-PVN oxytocin receptor blockade with L-368,899 (3 and 9 nmol) reduced restraint stress-evoked tachycardia and sympathetic/parasympathetic LF/HF ratio (p<0.05) and prevented late anxiety at 9 nmol.
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