Effect of 2-aminophosphonoheptanoic acid on the EEG of rats exposed to high pressure.

Excitatory amino acid neurotransmission may be involved in the tremor component of the high pressure neurological syndrome (HPNS). 2-Amino-7-phosphonoheptanoic acid (2-APH) is a novel antagonist of excitatory amino acids with preferential activity at the N-methyl-D-aspartate receptor. Rats were injected either i.p. or intracerebroventricularly with 2-APH and subsequently exposed to pressure. The EEG changes that occur after treatment with 2-APH at 1 ATA, namely, a marked increase in delta waves (1-4 Hz) in the centro-occipital region, continue at pressure. However, the apparent duration of action of 2-APH is shorter: the power spectra of delta waves reached its maximum value after a mean time of 37 min (SD 12) compared with 60 min (SD 5) in unpressurized rats. Behavioral results include an increase in the onset pressure for tremor--82.6 ATA (SEM 4.7) in treated rats compared with 49.4 ATA (SEM 3.4) in saline controls (P less than 0.005). It is probable that the antitremor effect and the EEG changes resulting from 2-APH are due to decreased postsynaptic activity of an excitatory neurotransmitter, and these data support the hypothesis that tremor may be central rather than peripheral in origin.