Cholecystokinin: critical role in mediating olfactory influences on reproduction

Our electrophysiological studies in female mice have demonstrated that electrical stimulation of the accessory olfactory bulb excites tuberoinfundibular dopaminergic arcuate neurons via the amygdala-stria terminalis route. This study shows that the medial preoptic area is identified as an additional relay for the excitatory transmission by examining the effectiveness of locally infused lignocaine anaesthetic in blocking the transmission and that of electrical stimulation in evoking a shorter latency response. Based on the known immunohistochemical findings, further attention is focused on a transmitter mediating synaptic transmission in the medial preoptic area. The cholecystokinin-B type receptor antagonist L-365,260 (0.3, 0.6, 0.9 pmol), but not the A type receptor antagonist L-364,718 (0.9 pmol), infused into the medial preoptic area, blocked the excitation of tuberoinfundibular arcuate neurons in a dose-dependent manner. Conversely, cholecystokinin octapeptide (0.6 pmol) increased firing activity in such neurons. The antagonizing effect of L-365,260 was reproduced in the context of the olfactory block to pregnancy: bilateral infusions of this drug into the medical preoptic area of recently mated females immediately before exposures to strange males' pheromones prevented them from inducing pregnancy block. These findings implicate cholecystokinin acting on cholecystokinin-B receptors in the medial preoptic area as a mediator of olfactory influences on reproductive physiology.