NMDA NR2 receptors participate in CCK-induced reduction of food intake and hindbrain neuronal activation

Feb 24, 2009Brain research

Certain Brain Receptors Help a Gut Hormone Reduce Eating and Activate Hindbrain Neurons

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Abstract

Intraperitoneal administration of D-CPPene increased intake of sucrose and rodent chow by up to 50% in a rodent model.

Blockade of NMDA receptors in the hindbrain is associated with increased food intake.
D-CPPene, a selective NMDA antagonist, reversed the appetite-suppressing effects of cholecystokinin (CCK).
Increased intake of palatable foods (sucrose and chow) occurred without a corresponding increase in non-nutrient consumption (saccharin).
The findings suggest that NMDA receptors outside the hindbrain may influence food intake regulation.
CCK-induced activation of neurons in the dorsal hindbrain is attenuated by D-CPPene treatment.

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Previous work has shown that blockade of NMDAR by non-competitive (MK-801) and competitive (AP5) antagonists increase food intake by acting in the dorsal hindbrain. NMDAR are heteromeric complexes composed of NR1, NR2 and NR3 subunits. Competitive NR2B antagonists potently increase feeding when injected into the hindbrain. NR2 immunoreactivity is present in the hindbrain, vagal afferents and enteric neurons. NMDA receptors expressed on peripheral vagal afferent processes in the GI tract modulate responsiveness to GI stimuli. Therefore, it is possible that peripheral as well as central vagal NMDA receptors participate in control of food intake. To examine this possibility, we recorded intake of rodent chow, a palatable liquid food (15% sucrose), and non-nutrient (0.2% saccharin) solutions following intraperitoneal (i.p.) administration of D-CPPene, a competitive NMDA receptor antagonist that is selective for binding to the NR2B/A channel subunit. To assess participation of peripheral NMDA receptors in postoral satiation signals, we examined the ability of D-CPPene to attenuate reduction of feeding and hindbrain Fos expression following IP CCK administration. IP D-CPPene (2, 3 mg/kg) produced a significant increase in sucrose and chow intake but not saccharin. Pretreatment with D-CPPene (2 mg/kg) reversed CCK (2 microg/kg)-induced inhibition of sucrose intake, and attenuated CCK-induced Fos-Li in the dorsal hindbrain. These results confirm that antagonism of hindbrain NMDA receptors increases food intake. In addition our results suggest that NMDA receptors outside the hindbrain, perhaps in the periphery, participate in vagally mediated, CCK-induced reduction of food intake and NTS neuron activation.

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NMDA NR2 receptors participate in CCK-induced reduction of food intake and hindbrain neuronal activation

Abstract

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