Intraventricular cycloheximide attenuates the restraint-induced long-lasting effect on plus maze exploration.

Rats submitted to 2 h of restraint stress show reduced open arm exploration in the elevated plus maze 24 h later. To determine if this effect is dependent on protein synthesis during or after the restraint period, cycloheximide, a protein synthesis inhibitor, was injected into the right cerebral ventricle of male Wistar rats (200-250 g), immediately before (N = 19 animals per group), immediately after (N = 7 animals per group) or 2 h (N = 10 animals per group) following a 2-h period of forced restraint. Twenty-four hours later the animals were tested in the elevated plus maze. Non-stressed control groups received saline (SAL, N = 8-9 per group) or cycloheximide (CHX, N = 8-9 per group) and were tested 1 h or 24 h later in the maze. Pre- but not post-stress microinjections of cycloheximide (20 micrograms in 2 microliters) increased exploration in the elevated plus maze (% of time spent in open arms, pre-stress injection: SAL = 4.6 +/- 1.2, CHX = 10.7 +/- 2.3; number of enclosed arms entries: SAL = 3.6 +/- 0.5, CHX = 5.6 +/- 0.4). No drug effect was observed in non-stressed animals. These results suggest that blockade of protein synthesis during the restraint period may attenuate the behavioral consequences of stress.