Extracellular GABA in the medial hypothalamus is increased following hypocretin-1 administration.
OBJECTIVE
Hypocretin 1 is an hypothalamic neuropeptide that induces an increase in food intake when administered into the cerebral lateral ventricle. As it is well known that the medial hypothalamus (MH) is involved in the feeding behaviour also through GABAergic circuits, the aim of this experiment was to investigate the effect of an hypocretin 1 intracerebroventricular (icv) injection on the extracellular levels of GABA in the MH.


METHODS
GABA levels in the MH were evaluated in six rats by microdialysis and high performance liquid chromatography-electrochemical detection 30 min before and every 30 min for an over all period of 6 h after an icv injection of hypocretin 1. The same procedure was used in another group of six rats but saline was injected into the lateral ventricle as control.


RESULTS
The results show that extracellular GABA increases in the MH after the injection of hypocretin 1 at 60 min and at 3 h after the injection.


CONCLUSIONS
This finding suggests a possible mechanism by which hypocretin 1 should induce hyperphagia in the first hour after injection. As it is already known that the inhibition of the MH by injection of GABA causes an increase of food intake, it is possible that hypocretin 1 causes an increase in food intake by increasing the GABA release in the MH. The lack of an increase in the GABA level after the fourth hour is consistent with the lack of an increase in food intake at this time, as we observed in previous experiments. The finding of a biphasic increase in the GABA level, at 60 min and at 3 h, was unexpected and should be further investigated.
Section of Human Physiology, Department of Experimental Medicine, Second University of Naples, Naples, Italy.
An
A
Viggiano
M
M
Monda
Al
A
Viggiano
F
F
Fuccio
B
B
De Luca
D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001831:Body Temperature / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D007033:Hypothalamus, Middle / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D008297:Male; D017551:Microdialysis / Q000379:methods; D009479:Neuropeptides / Q000008:administration & dosage*; D018377:Neurotransmitter Agents / Q000008:administration & dosage; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000032:analysis*
C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D000068797:Orexins; D005680:gamma-Aminobutyric Acid