INTRASEPTAL INFUSION OF SELECTIVE AND COMPETITIVE GLUTAMATE-RECEPTOR AGONIST NMDA AND ANTAGONIST D-2-AMINO-5-PHOSPHONOPENTANOIC ACID - SPECTRAL IMPLICATIONS FOR THE PHYSOSTIGMINE-INDUCED HIPPOCAMPAL THETA-RHYTHM IN URETHANE-ANESTHETIZED RATS

Theta (theta) rhythm may be mediated, at least in part, by a glutamate neurotransmitter. Thus, in the present study, it was hypothesized tha t the septum glutamatergic NMDA receptor subtype may be involved in th e modulation of physostigmine-induced theta rhythm. To test this hypot hesis, we analyzed, in the urethane-anesthetized rat, the effects of s eptum application of NMDA and D-2-amino-5-phosphonopentanoic acid (AP5 ), selective and competitive NMDA agonist and antagonist, respectively , on the spectral characteristics of hippocampal theta rhythm elicited by intravenous injection of a anticholinesterase agent, physostigmine . A low dose (16 nmol) of AP5 did not significantly affect EEG recordi ngs, whereas a high dose (50.75 nmol) resulted in significant decrease s in phase (-61.8%) at theta frequency, peak theta power (-64.2%), and absolute power of the low-frequency theta band (-67%). These electroe ncephalographic alterations, which appeared at 50.75 nmol AP5, were am plified following application of massive doses of the drug (121.8 nmol , n=1, and 162 nmol, n=1). Amplification, however, was slight and the theta waves remained clearly detectable. On the other hand, the infusi on of NMDA resulted in a significant increase in frequency (+25%) of t his rhythm, but this effect was completely antagonized by prior local administration of 16 nmol AP5. Our data suggest that the septal NMDA r eceptors exert subtle modulatory influences on the septohippocampal ce lls involved in physostigmine-induced theta wave production, which has not been reported elsewhere: tonic with respect to both low-frequency theta band power and theta phase, and phasic with respect to theta fr equency. Our data also indicate that the septum may be a sensitive act ion site for exogenously administered glutamatergic drugs.