Role of N-Methyl-D-Aspartate (NMDA) Receptors in Vasopressin and Oxytocin Responses to Emotional Stimuli

Abstract

Vasopressin (VP) release by the neurohypophysis is suppressed and oxytocin (OT) release is augmented after conditioned or unconditioned fear stimuli(3) and after anxiety-producing novel environmental stimuli (2, 4). The NMDA subtype of glutamate receptor is essential for long-term potentiation of excitatory synaptic transmission in the hippocampus and, thereby, has been postulated to play a crucial role in learning and memory. Behavioural experiments have shown that an NMDA-receptor antagonist injected in the amygdala impairs acquisition but not retention or recall of emotional memory associated with conditioned fear response(1). Thus, the present study aimed at investigating in male rats after overnight water deprivation whether an i.p. administered NMDA-receptor antagonist, MK-801 impairs the VP, OT and prolactin (PRL) responses to emotional stimuli. In the experiments with conditioned fear stimuli, rats were trained with environmental stimuli paired with footshocks and tested with the environmental stimuli on the following day. MK-801 administered 30 min before training impaired the suppressive VP and the augmentative OT and PRL responses to conditioned fear stimuli (Fig. 1A). The antagonist injected after training, however, did not block the hormonal responses (data not shown). MK-801 given before testing stimuli abolished the VP and PRL responses and reduced the OT response to conditioned fear stimuli (Fig. 1B). The blocking action of the drug was not due to a reduced level of emotional arousal, since the VP, OT and PRL responses to unconditioned fear stimuli (Fig. 1C) or novel environmental stimuli (Fig. 1D) were not impaired by the drug.