Behavioral effects of d-cycloserine in rats: The role of anxiety level

It has been reported that the glutamatergic N-methyl-d-aspartate (NMDA) receptor is involved in stress responses and that anxiety is the primary response to stress. Although individual differences in anxiety levels of rats have been demonstrated by using the elevated plus-maze (PM) test, the role of NMDA receptor activity in such individuality of anxiety is not clear. Here, we examined whether low (LA) and high (HA) anxiety rats might respond differently to treatment with d-cycloserine (DCS), a partial agonist of the glycine binding site located on NMDA receptors. Male Wistar rats were screened by using the PM and divided into LA and HA subgroups. On the next day, these rats were again tested in the PM, 30 min after the treatment with DCS (5, 10, or 30 mg/kg ip). Five days later, the rats were subjected to a 2-day forced swim (FS) test, receiving the DCS treatment again 30 min before the second day session. The PM data showed that DCS had anxiogenic effects in LA but not HA rats. The immobility of LA or HA rats in the FS test was not affected by DCS. The results indicate that the behavioral effects of DCS depend on the anxiety level of rats and have task-dependent behavioral consequences, suggesting that glycine binding sites on NMDA receptors are involved in individual differences of anxiety level.