Visceral afferent participation in delayed satiation following NMDA receptor blockade.
We previously reported that rats increase their food intake, but not water intake, following intraperitoneal (i.p.) injection of MK-801, a noncompetitive antagonist of N-methyl-D-aspartate (NMDA)-activated ion channels. The drug appears to specifically interfere with signals that participate in satiation, thereby prolonging the meal and increasing its size. The mechanism by which delayed satiation occurs is not known. However, some well-studied satiety signals are carried by visceral sensory fibers that innervate the abdominal viscera. We hypothesized that MK-801 might increase food intake by interfering with satiety signals transmitted by visceral afferent neurons. To test this hypothesis, we examined MK-801's effect on food intake in rats systemically treated with capsaicin, a neurotoxin that destroys small unmyelinated visceral afferent neurons. Capsaicin treatment significantly attenuated increased sucrose intake following MK-801. We also investigated whether the effects of MK-801 on food intake would persist in rats treated with total subdiaphragmatic vagotomies. MK-801 increased the intake of 15% sucrose by sham-vagotomized rats, while vagotomized rats did not increase their intake following MK-801. Taken together, these results support the hypothesis that capsaicin-sensitive visceral sensory neurons are involved in increased food intake following systemic NMDA receptor blockade. This, in turn, suggests that NMDA receptor activation may be an important component of the neural circuitry involved in satiation.
Burns
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GA
College of Veterinary Medicine, Department of VCAPP, Washington State University, Pullman, 99164-6520, USA. gil_burns@wsu.edu
Ritter
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RC
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D009412:Nerve Fibers / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012528:Satiety Response / Q000502:physiology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D002211:Capsaicin