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 that the septum glutamatergic NMDA receptor subtype may be involved in the modulation of physostigmine-induced theta rhythm. To test this hypothesis, we analyzed, in the urethane-anesthetized rat, the effects of septum 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 recordings, whereas a high dose (50.75 nmol) resulted in significant decreases in phase (-61.8%) at theta frequency, peak theta power (-64.2%), and absolute power of the low-frequency theta band (-67%). These electroencephalographic alterations, which appeared at 50.75 nmol AP5, were amplified 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 infusion of NMDA resulted in a significant increase in frequency (+25%) of this rhythm, but this effect was completely antagonized by prior local administration of 16 nmol AP5. Our data suggest that the septal NMDA receptors exert subtle modulatory influences on the septohippocampal cells 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 frequency. Our data also indicate that the septum may be a sensitive action site for exogenously administered glutamatergic drugs.