LEAN (FA FA) BUT NOT OBESE (FA/FA) ZUCKER RATS RELEASE CHOLECYSTOKININ AT PVN AFTER A GAVAGED MEAL/

Neuropeptides play an important role in the integration of dietary sig nals. Cholecystokinin (CCK) has been implicated in regulating ingestiv e behavior, particularly satiety. The primary objective of this study was to examine whether the hyperphagia characteristic of obese (fa/fa) rats involves impaired neural CCK secretion. Dynamic release of CCK a t the hypothalamic paraventricular nucleus (PVN) of age-matched lean ( Fa/Fa) and obese Zucker rats was determined using push-pull perfusion. The gavage of a 10.3-kcal (6 mi) liquid diet during lights off was fo llowed by increased CCK release in lean rats (from 13.6 +/- 1.1 to 22. 1 +/- 1.4 fmol in the Ist postprandial period and 18.4 +/- 2.5 fmol in the 2nd postprandial period). An identical meal load resulted in no p ostprandial increase in CCK release in obese rats, despite the fact th at high-K+ artificial cerebrospinal fluid evoked CCK outflow in all an imals. Intubation of 6 mi of nonnutritive 1% carboxymethylcellulose ha d no effect. These results are consistent with the suggestion that hyp othalamic CCK plays a physiological role in satiety, and they demonstr ate that obese Zucker rats have blunted hypothalamic CCK release in re sponse to dietary cues.