Submitted on May 28, 2008
Revised on February 2, 2009
Accepted on February 2, 2009
Blockade of hindbrain NMDA receptors containing NR2 subunits increases sucrose intake
Doug B Guard1, Timothy David Swartz1, Robert C. Ritter2, Gilbert A Burns3, and Mihai Covasa1*
1 The Pennsylvania State University
2 Washington State University
3 Ross University
* To whom correspondence should be addressed. E-mail: mzc13{at}psu.edu.
We have previously shown that blockade of N-methyl-D-aspartate (NMDA) receptors in the caudal brainstem delays satiation and increases food intake. NMDA receptors are heterodimers made up of distinct, but different, ion channel subunits. The NR2 subunits of the NMDA receptor contain the binding site for glutamate. About half of vagal afferents express immunoreactivity for NMDA NR2B subunit and about half of the NR2B expressing afferents also express NMDA NR2C or NR2D subunits. This suggests that increased meal size may be evoked by interference with glutamate binding to NMDA channels containing the NR2B subunit. To test this, we measured deprivation-induced intake of 15% sucrose solution following fourth ventricle and intra-NTS injections of Conantokin-G (NR2B blocker), D-CPPene (NR2B/2A blocker) and PPDA (NR2D/C blocker). Fourth ventricular administration of ConG (5, 20, 40, 80ng), D-CPPene (3.0, 6.25, 12.5, 25, 50, 100ng) and PPDA (300, 400 ng) increased sucrose intake significantly compared to control. Likewise, injections of Con G (10ng), D-CPPene (5ng, 10ng) and PPDA (0.5, 1.0, 2.5, 5.0ng) directly into the NTS produced significant increases in sucrose intake. These results show that hindbrain injection of competitive NMDA antagonists with selectivity or preference for the NMDA receptor NR2B or NR2C subunits increase food intake.
