Central Cholecystokinin‐Octapeptide Accelerates the Activity of the Hypothalamic Gonadotropin‐Releasing Hormone Pulse Generator in Goats

To clarify central actions of cholecystokinin-octapeptide (CCK-8) on reproduction, effects of an intracerebroventricular (i.c.v.) administration of CCK-8 on the activity of the gonadotropin-releasing hormone (GnRH) pulse generator were examined in ovariectomized (OVX) goats in the absence or presence of oestradiol. Goats were chronically fitted with recording electrodes in the mediobasal hypothalamus, and electrophysiological manifestations of the GnRH pulse generator were monitored as characteristic increases in the multiple-unit activity (MUA volleys). In OVX goats, a bolus i.c.v. injection of as little as 0.01 nmol of CCK-8 induced a MUA volley with a short latency, which resulted in a significant decrease in the post-treatment volley interval compared to that in the saline injected control. Administration of higher doses of CCK-8 (0.1 and 2 nmol) did not further accelerate the occurrence of the MUA volley, but stimulatory effects were observed for a longer period than that after the 0.01 nmol injection. When goats were treated with oestradiol, while a bolus i.c.v. injection of 0.01 nmol CCK-8 had no effect, an injection of 0.1 nmol of the peptide significantly decreased the post-treatment volley interval. On continuous i.c.v. infusion of CCK-8 at 3 nmol per 200 μl/h for 3 h, MUA volleys with shorter intervals than those in the control were successively induced without any apparent change in basal plasma luteinizing hormone levels in OVX goats. These results demonstrate that central CCK-8 strongly accelerates the activity of the GnRH pulse generator in goats.