The lateral hypothalamus: a primary site mediating excitatory amino acid-elicited eating.

Lateral hypothalamic (LH) injections of the excitatory neurotransmitter glutamate, or its excitatory amino acid (EAA) agonists, kainic acid (KA), D,L-alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid (AMPA), or N-methyl-D-aspartic acid (NMDA), can rapidly elicit an intense feeding response in satiated rats. To determine whether the LH is the actual locus of this effect, we compared these compounds' ability to stimulate feeding when injected into the LH, versus when injected into sites bracketing this region. Food intake in groups of adult male rats was measured 1 h after injection of glutamate (30-900 nmol), KA (0.1-1.0 nmol), AMPA (0.33-3.3 nmol), NMDA (0.33-33.3 nmol) or vehicle, through chronically implanted guide cannulas, into one of seven brain sites. These sites were: the LH, the anterior and posterior tips of the LH, the thalamus immediately dorsal to the LH, the amygdala just lateral to the LH, or the paraventricular and perifornical areas medial to the LH. The results show that across doses and agonists the eating-stimulatory effects were largest with injections into the LH. In the LH, glutamate between 300 and 900 nmol elicited a dose-dependent eating response of up to 5 g within 1 h (P < 0.01). Each of the other agonists at doses of 3.3 nmol or less elicited eating responses of at least 10 g with injections into this site. Injections into the other brain sites produced either no eating, or occasionally smaller and less consistent eating responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Lateral hypothalamic injections of glutamate, kainic acid, D,L-alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid or N-methyl-D-aspartic acid rapidly elicit intense transient eating in rats.

A convergence of evidence suggests that stimulation of lateral hypothalamic (LH) neurons can elicit eating, but the neurotransmitters that mediate this effect are unknown. To determine whether glutamate might be involved, it was injected through chronic guide cannulas directly into the LH of satiated adult male rats and consequent food intake was measured. Glutamate produced a dose-dependent eating response (mean intakes of 3.7 g at 300 nmol and 5.2 g at 900 nmol) only within the first hour after injection. As a first step in determining the receptor types mediating this response, agonists for specific excitatory amino acid (EAA) receptors were similarly tested. Kainic acid (KA), D,L-alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid (AMPA) or N-methyl-D-aspartic acid (NMDA) injected into the LH each elicited eating in a dose-dependent fashion beginning at 0.33 to 1.0 nmol. At maximally effective doses (1.0-33 nmol), each agonist elicited food intakes of approximately nine grams within 1 h. Finally, analysis of meal and behavioral patterns produced by LH injection of glutamate (600 nmol) and KA (1.0 nmol) revealed that the elicited eating usually began 2-3 min postinjection and consisted of a single normal to large size meal. There were no other behavioral effects during this initial postinjection period and no effects on other oral behaviors, like drinking or gnawing, at any time. Collectively, these findings suggest that glutamate may act through several subtypes of its receptors on some LH neurons to elicit eating.