NEUROPEPTIDE-Y RELEASE IN THE PARAVENTRICULAR NUCLEUS IS DECREASED DURING TRANSIENT HYPERPHAGIA INDUCED BY MICROINJECTION OF COLCHICINE INTO THE VENTROMEDIAL NUCLEUS OF RATS

Disruption of neural signaling in the ventromedial nucleus (VMN) of ra ts by microinjection of the neurotoxin colchicine (COL) results in tra nsient hyperphagia accompanied by enhanced weight gain. We tested the hypothesis that release of neuropeptide Y (NPY), a potent orexigenic s ignal is augmented within the paraventricular nucleus (PVN) of COL-tre ated hyperphagic rats. Adult male rats were microinjected bilaterally with either COL (4 mu g/0.5 mu l in saline) or saline in the VMN and a push-pull guide cannula aimed at the PVN was implanted for analysis o f extra-cellular NPY. COL-injected rats gained 37.8 +/- 6.1 g while th e saline-injected rats lost 9.3 +/- 3.4 g during the 4 days following surgery. On day 4, post-injection, the PVN of these rats was perfused with artificial cerebrospinal fluid via the push-pull cannula. NPY lev els in perfusates collected at 10 min intervals from hyperphagic, COL- injected rats were markedly diminished. Cumulative NPY efflux over the 180 min sampling period was significantly less in COL-treated (27.7 /- 6.0 pg) versus saline-injected control rats (110.6 +/- 32.2 pg; P < 0.05). These results show that impairment of neural signaling in the VMN by COL suppressed NPY release in the PVN. These observations taken together with previous studies showing diminution in preproNPY mRNA i n the arcuate nucleus (ARC) and NPY levels in the PVN are in accordanc e with the thesis that the VMN normally exerts a facilitatory influenc e on NPYergic signaling in the ARC-PVN axis. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.