Reverse microdialysis of N-methyl-D-aspartic acid into the lateral hypothalamus of rats: effects on feeding and other behaviors.

The effects of reverse microdialysis of N-methyl-D-aspartic acid (NMDA) into the lateral hypothalamus (LH) on feeding and other behaviors were examined. Consistent with similar studies utilizing central microinjections, NMDA reverse microdialysed into the rat LH rapidly elicited a strong concentration-dependent stimulation of feeding. The minimum perfusate concentration of NMDA needed to elicit feeding with reverse microdialysis was 660 microM, a concentration 1/50 of that needed with pressure injections. Further, eating responses could be consistently elicited in sequential tests separated by 2-4 h in the same subject, and the magnitude of the eating in the first and second tests was highly correlated (r=0.87). Behavioral analysis revealed that the main response to NMDA consisted of eating without the concomitant hyperactivity produced by central microinjections of this agonist. The other behaviors exhibited during NMDA administration were those that normally occur during spontaneous feeding in rats. Also, rats precisely compensated for the increased food intake elicited by NMDA by reducing spontaneous feeding during the subsequent nocturnal phase, so as to maintain normal daily intakes. In contrast, N-methyl-L-aspartate (NMLA) reverse microdialysed in to the LH (660 microM) did not elicit feeding nor affect any other behaviors we examined. These data support a role for LH glutamate and NMDA receptors in the control of feeding.