The Lateral Hypothalamus: A Locus for GABAA Receptor Modulation of Feeding in the Rat

The goal of the present study was to determine whether the lateral hypothalamus (LH) is a specific site for feeding produced by injection of GABAA receptor (GABAAR) antagonists. Two cannula‐mapping studies were performed in which the GABAAR antagonist picrotoxin (PIC) was injected into LH or surrounding sites. In the first experiment, adult male rats with indwelling unilateral guide cannulas in the lateral preoptic area, dorsal medial hypothalamus, internal capsule/entopeduncular nucleus, thalamus, ventral tegmental area or LH were injected with 0.3ul aCSF vehicle or PIC (10 ng, 20 ng or 80 ng/0.3 ul veh) and food intake was measured 30 min to 4 h post‐injection. We found that, of the six sites tested, only LH injection of 80 ng PIC elicited significant feeding, with mean intakes of 5 g in 30 min versus under 1 g in surrounding sites. In the second experiment animals with unilateral cannulas in the tuberal LH (tLH) or sites 1 mm anterior or posterior to the tLH were injected with aCSF or PIC. We found that 80 ng PIC elicited eating only in tLH, with an intake of 4.2 g in 30 min, whereas little or no feeding was elicited in either anterior or posterior sites. Finally, to determine if LH is a site where natural feeding can be suppressed by activation of GABAAR, we injected the GABAAR agonists, muscimol or isoguvacine, through bilateral cannulas targeted at LH. Muscimol suppressed spontaneous feeding at the onset of the nocturnal phase of the photoperiod and also feeding in 24 h fasted rats. Isoguvacine similarly suppressed nocturnal eating but was ineffective in fasted rats. Collectively, these data provide evidence that LH is a major locus at which blockade of GABAA receptors can disinhibit eating and where activation of these receptors can suppress natural eating.