Influence of age and of pre‐treatment with D‐cycloserine on the behavior of ethanol‐treated rats tested in the elevated plus‐maze apparatus

Abstract

There is evidence that ethanol is able to influence central functions through the antagonism of the NMDA-receptor system. It has been shown that this system is also involved in the modulation of anxiety-related behavior in rats. Recently, we observed gender- and age-related behavioral influences in rats tested on the elevated plus-maze apparatus The present study was undertaken in order to investigate: (1) the effects of ethanol (0.8, 1.0 or 1.2 g/kg, i.p.) on the behavior of male and female rats tested on the elevated plus-maze at 2, 3, 4 or 5 months of age; (2) the effect of the pre-treatment with D-cycloserine (3.0 or 6.0 mg/kg), an agonist of the glutamate NMDA-receptor system, 30 min before the ethanol (1.2 g/kg) injections, in rats tested in the elevated plus-maze at 2 months or 4 months of age. The results demonstrated that ethanol did not affect the time spent and the frequency of entries on the open arms of the elevated plus-maze in rats tested at 2 months of age, but increased these parameters in older animals. Moreover, the results showed that D-cycloserine, at doses that did not affect the behavior of control animals, antagonized the increased frequency of entries and time spent on open arms produced by ethanol in rats tested at 4 months of age. Our results suggest an age-related influence on the anxiolytic action of ethanol in rats tested in the elevated plus-maze. Moreover, the results suggest that the NMDA-receptor system can be involved in this effect, and strengthens the evidence for the participation of the NMDA-receptor system in anxiety-related behavior.

Experimental anxiety and the reinforcing effects of ethanol in rats

“…Although not tested in the present investigation, it is important to emphasize that studies in this laboratory using EtOH in a quite similar dosage range (0.8-1.2 g/kg, ip) did not find differences in anxiety measurements recorded in the plus-maze test (25). Therefore, it is likely that the results of place preference conditioning were not confounded by the potential anxiolytic effect of EtOH.…”

Postinjury weight rather than cognitive or behavioral impairment predicts development of posttraumatic epilepsy after lateral fluid‐percussion injury in rats

“…In all animal groups, however, we found a significant reduction in all test parameters at 4 months compared with that at 1 month, which is possibly related to aging, as described previously. 37,38 It is also possible that the re-test effect affected the performance in the second test despite of about 3 months interval between the tests.…”

NMDA Antagonists and Tolerance to Drugs Affecting the Central Nervous System

“…D-cycloserine (DCS), a partial agonist at the glycine site of the NMDA receptor, blocked the anxiolytic effect of ethanol in rats tested in the elevated plus-maze (21). The anxiolytic effect produced by HA-966 [(±)-3-amino-1-hydroxy-2-pyrrolidone], a drug acting as an antagonist at the glycine site in NMDA receptor, was similarly blocked by previous treatment with DCS, suggesting that ethanol and HA-966 may share similar mechanisms of anxiolytic action (20).…”