2005 - HINDBRAIN ADMINISTRATION OF NMDA RECEPTOR ANTAGONIST AP-5 INCREASES FOOD INTAKE IN THE RAT.
ADMINISTRATION OF NMDA RECEPTOR ANTAGONIST AP-5 INCREASES FOOD INTAKE IN THE RAT.
Hung CY, Covasa M, Ritter RC, Burns GA.
Nutritional Sciences, The Pennsylvania State University, University Park, PA, USA.
Hindbrain administration of MK-801, a non-competitive NMDA channel blocker, increases meal size, suggesting NMDA receptors in this location participate in control of food intake. However, MK-801 reportedly antagonizes some non-NMDA ion channels. Therefore, to further assess hindbrain NMDA receptor participation in food intake control, we measured deprivation-induced intakes of 15% sucrose solution or rat chow following intraperitoneal (IP), 4(th) ventricular (4V), or nucleus of the solitary tract (NTS) injection of either saline vehicle or D(-)-2-Amino-5-phosphonopentanoic acid (AP5), a competitive NMDA receptor antagonist. IP AP5 (0.05, 0.1, 1.0, 3.0 and 5.0mg/kg) did not alter 30-min sucrose intake at any dose (10.7 +/- 0.4 ml, saline control) (11.0 +/- 0.8, 11.2 +/- 1.0, 11.2 +/- 1.0, 13.1 +/- 2.2, and 11.0 +/- 1.9ml, AP5 doses, respectively). Fourth ventricular administration of both 0.2 microg (16.7 +/- 0.6 ml) and 0.4microg (14.9 +/- 0.5 ml) but not 0.1 and 0.6 microg of AP5 significantly increased 60-min sucrose intake compared to saline (11.2+/-0.4ml). 24-hr chow intake also was increased compared to saline (31.5 +/- 0.1g, AP5 vs. 27.1 +/- 0.6g saline). Furthermore, rats did not increase intake of 0.2% saccharin following fourth ventricular AP5 administration (9.8 +/- 0.7ml, AP5 vs 10.5 +/- 0.5ml, saline). Finally, NTS AP5 (20ng/30nl) significantly increased 30- (17.2 +/- 0.7 ml, AP5 vs 14.6 +/- 1.7 ml, saline), and 60-min (19.4 +/- 0.6 ml, AP5 vs. 15.5 +/- 1.4 ml, saline) sucrose intake, as well as 24-hr chow intake (31.6 +/- 0.3g, AP5 vs. 26.1 +/- 1.2g, saline).
These results support the hypothesis that hindbrain NMDA receptors participate in control of food intake, and suggest that this participation also may contribute to control of body weight over a 24-hr period.
PMID: 16269572 [PubMed - as supplied by publisher]
ncbi.nlm.nih.gov |