Research Report Stimulation of lateral hypothalamic kainate receptors selectively elicits feeding behavior Stacey R. Hettes a , Theodore W. Heyming, B. Glenn Stanley b,c, ⁎ a Department of Biology, Wofford College, Spartanburg, SC 29303, USA b Department of Psychology, University of California-Riverside, Riverside, CA 92521, USA c Department of Cell Biology and Neuroscience, University of California-Riverside, Riverside, CA 92521, USA ARTICLE INFO ABSTRACT Article history: Accepted 24 September 2007 Available online 2 October 2007 Glutamate and its receptor agonists, NMDA, AMPA, and KA, elicit feeding when microinjected into the lateral hypothalamus (LH) of satiated rats. However, determining the relative contributions of AMPA receptors (AMPARs) and KA receptors (KARs) to LH feeding mechanisms has been difficult due to a lack of receptor selective agonists and antagonists. Furthermore, LH injection of KA produces behavioral hyperactivity, questioning a role for KARs in feeding selective stimulation. In the present study, we used the KAR agonist, (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), which selectively binds the GluR5 subunit of KARs, to stimulate feeding, presumably via KAR activation. Using ATPA, we tested whether: (1) LH injection of ATPA elicits feeding, (2) prior treatment with the non-selective AMPA/KAR antagonist, CNQX, suppresses ATPA-elicited feeding, and (3) LH injection of ATPA elicits behavioral patterns specific for feeding. We found that injection of ATPA (0.1 and 1 nmol) elicited an intense feeding response (e.g., 4.8 ± 1.6 g) that was blocked by LH pretreatment with CNQX, but was unaffected by pretreatment with the AMPAR selective antagonist, GYKI 52466. Furthermore, minute-by-minute behavioral analysis revealed that LH injection of ATPA increased time spent feeding to 55% of the initial test period with little or no effects on other behaviors at any time. In contrast, LH injection of KA similarly increased feeding but also produced intense locomotor activity. These data suggest that selective activation of LH KARs containing GluR5 subunit(s) is sufficient to elicit feeding. © 2007 Elsevier B.V. All rights reserved. Keywords: Lateral hypothalamus Feeding Kainate Glutamate ATPA iGluR 1. Introduction One of our major goals has been to determine the role of LH glutamate in the stimulation of feeding behavior. Toward this end, we have employed agonists of N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxale propionate (AMPA), and kainate (KA) receptors to provide evidence that these ionotropic glutamate receptor (iGluR) subtypes may play a role in feeding stimulation (Duva et al., 2002; Hettes et al., 2003; Khan et al., 1999; Stanley et al., 1993a,b, 1996). Addi- tionally, we have demonstrated that LH pretreatment with the NMDA receptor (NMDAR) antagonist, D(−)-2-amino-5- phosphonopentanoic acid (DAP-5), blocked food intake eli- cited by subsequent LH injection of NMDA without affecting BRAIN RESEARCH 1184 (2007) 178 – 185 ⁎ Corresponding author. Department of Psychology, University of California-Riverside, Riverside, CA 92521, USA. Fax: +1 951 827 3985. E-mail address: glenn.stanley@ucr.edu (B.G. Stanley). 0006-8993/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2007.09.060 available at www.sciencedirect.com www.elsevier.com/locate/brainres