Glutamate and GABA in lateral hypothalamic mechanisms controlling food intake

By the 1990s a convergence of evidence had accumulated to suggest that neurons within the lateral hypothalamus (LH) play important roles in the stimulation of feeding behavior. However, there was little direct evidence demonstrating that neurotransmitters in the LH could, like electrical stimulation, elicit feeding in satiated animals. The present paper is a brief review in honor of Bartley Hoebel's scientific contributions, emphasizing the evidence from my lab that the excitatory neurotransmitter glutamate and the inhibitory neurotransmitter gamma aminobutyric acid (GABA) in the LH mediate feeding stimulation and feeding inhibition respectively. Specifically, we summarize evidence that LH injection of glutamate, or agonists of its N-methyl-d-aspartate (NMDA) and non-NMDA receptors, elicits feeding in satiated rats, that NMDA receptor antagonists block the eating elicited by NMDA and, more importantly, that NMDA blockade suppresses natural feeding and can reduce body weight. Conversely, GABAA agonists injected into the LH suppress feeding and can also reduce body weight, while GABAA receptor antagonists actually elicit eating when injected into the LH of satiated rats. It is suggested that natural feeding may reflect the moment-to-moment balance in the activity of glutamate and GABA within the LH.

► Lateral hypothalamic (LH) injections of glutamate or NMDA elicit feeding behavior. ► LH NMDA receptor antagonists suppress deprivation induced and nocturnal feeding. ► LH NMDA receptor antagonist suppresses feeding induced by neuropeptide Y. ► LH injection of GABAA receptor agonist suppresses and antagonists elicit feeding. ► Feeding may result from the balance of glutamate and GABA activity in the LH.