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-aspar tate receptor system. Recent in vitro evidence reveals that N-methyl-D -aspartate receptor activation dramatically alters the spontaneous dis charge patterns of supraoptic neurons. In this study we evaluate wheth er N-methyl-D-aspartate receptors in vivo contribute to the developmen t of characteristic phasic discharge patterns displayed by vasopressin -secreting neurons. Intravenous administration of ketamine hydrochlori de, a non-competitive N-methyl-D-aspartate receptor antagonist, was us ed to examine whether N-methyl-D-aspartate receptor blockade influence s patterned spontaneous discharge observed in supraoptic neurosecretor y neurons. Extracellular recordings were obtained from identified hypo thalamic supraoptic neurons in pentobarbital-anaesthetized Long-Evans rats. Systemic administration of ketamine (less than or equal to 1.5 m g/kg) potently suppressed spontaneous phasic discharge in 16/19 putati ve vasopressin-secreting cells. The ketamine-induced blockade was dose dependent, fully reversible and was associated with the complete bloc kade of activity evoked by local pressure application of N-methyl-D-as partate, but not the activity evoked by ha-amino-3-hydroxy-5-methyl-is oxazole-4-propionate receptor agonists (6/6 cells). Ketamine had no de tectable effect on threshold or shape of antidromic action potentials. By comparison, the activity in 9/10 continuously active neurons (puta tive oxytocin-secreting) was unaffected by administration of identical doses of ketamine. These data suggest that N-methyl-D-aspartate recep tors play an important role in regulating the onset and maintenance of spontaneous phasic activity patterns displayed by rat supraoptic vaso pressin neurons in vivo.