N-methyl-D-aspartate receptor antagonist ketamine selectively attenuates spontaneous phasic activity of supraoptic vasopressin neurons in vivo.
Supraoptic neurosecretory neurons express a prominent N-methyl-D-aspartate receptor system. Recent in vitro evidence reveals that N-methyl-D-aspartate receptor activation dramatically alters the spontaneous discharge patterns of supraoptic neurons. In this study we evaluate whether N-methyl-D-aspartate receptors in vivo contribute to the development of characteristic phasic discharge patterns displayed by vasopressin-secreting neurons. Intravenous administration of ketamine hydrochloride, a non-competitive N-methyl-D-aspartate receptor antagonist, was used to examine whether N-methyl-D-aspartate receptor blockade influences patterned spontaneous discharge observed in supraoptic neurosecretory neurons. Extracellular recordings were obtained from identified hypothalamic supraoptic neurons in pentobarbital-anaesthetized Long-Evans rats. Systemic administration of ketamine (< or = 1.5 mg/kg) potently suppressed spontaneous phasic discharge in 16/19 putative vasopressin-secreting cells. The ketamine-induced blockade was dose dependent, fully reversible and was associated with the complete blockade of activity evoked by local pressure application of N-methyl-D-aspartate, but not the activity evoked by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptor agonists (6/6 cells). Ketamine had no detectable effect on threshold or shape of antidromic action potentials. By comparison, the activity in 9/10 continuously active neurons (putative oxytocin-secreting) was unaffected by administration of identical doses of ketamine. These data suggest that N-methyl-D-aspartate receptors play an important role in regulating the onset and maintenance of spontaneous phasic activity patterns displayed by rat supraoptic vasopressin neurons in vivo.
Nissen
R
R
Neuroscience Unit, Loeb Research Institute, Ottawa Civic Hospital, Ontario, Canada.
Hu
B
B
Renaud
L P
LP
D000818:Animals; D004594:Electrophysiology; D007275:Injections, Intravenous; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013495:Supraoptic Nucleus / Q000502:physiology*; D014667:Vasopressins / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D016194:Receptors, N-Methyl-D-Aspartate; D014667:Vasopressins; D007649:Ketamine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid