Psychotropic activity of N-methyl-2-amino-4-phosphonobutyric acid (N-methyl AP4).

We have previously reported that 2-amino-4-phosphonobutyric acid (AP4), an agonist of presynaptically located metabotropic glutamate receptors, administrated at a single intracerebroventricular (icv) injection facilitated learning and memory in a passive- and learning in an active avoidance situation, enhanced apomorphine stereotypy, and attenuated haloperidol catalepsy in rats. In the present study the effect of a single icv injection of N-methyl analogue of AP4 (N-methyl AP4), in the same behavioral tests was investigated in rats. The compound at the doses of 100 and 200 micrograms per rat significantly enhanced apomorphine stereotypy, at the dose of 75 micrograms per rat attenuated haloperidol-induced catalepsy, without having any influence on spontaneous locomotor activity estimated in the open field test. N-methyl AP4 at the doses of 75 and 100 micrograms per rat significantly facilitated acquisition of information, consolidation, and retrieval process in a passive avoidance situation. The compound significantly improved only acquisition of conditioned avoidance responses (CARs) at the doses of 50 and 75 micrograms per rat; the positive effect of N-methyl AP4 on consolidation and recall of CARs was insignificant. Methyl-substitution at N-position in AP4 did not change its effects in the performed behavioral tests.