Interaction of the hypocretins with neurotransmitters in the nucleus accumbens.
The hypocretins (hcrt1 and hcrt2), also known as orexins, are two neuropeptides derived from the same precursor, expressed in a few thousand cells in the lateral hypothalamus. Hypocretin-containing cells project throughout the brain, including ascending projections to the olfactory bulb and cerebral cortex, through the medial septum and the nucleus accumbens. Here, we have studied the interactions of the hypocretins with different neurotransmitters by patch clamp recording of acutely dissociated cells from the nucleus accumbens. Application of hcrt1 or hcrt2 decreased postsynaptic NMDA currents, enhanced GABA currents but did not affect glycine-activated conductances. Our results strongly suggest that the hypocretin peptides may be inhibitory peptides, probably via binding hcrt receptor 2.
Martin
Gilles
G
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Fabre
Véronique
V
Siggins
George R
GR
de Lecea
Luis
L
D000200:Action Potentials; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004347:Drug Interactions / Q000502:physiology; D004594:Electrophysiology / Q000379:methods; D005998:Glycine / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D016202:N-Methylaspartate / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000378:metabolism* / Q000502:physiology; D064446:Orexin Receptors; D000068797:Orexins; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000096:biosynthesis; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D005998:Glycine