Intra-hippocampal administration of cycloheximide attenuates the restraint-induced exploratory deficit of an elevated plus maze

Abstract

Rats submitted to 2 h of restraint stress show a reduced open arm exploration in the elevated plus maze 24 h later. The stress-induced exploratory deficit is prevented by i.c.v. pre-stress administration of cycloheximide (CHX), a protein synthesis inhibitor. The objective of the present work was to determine if the hippocampus could be involved in this effect. CHX (4 or 8 μg) was injected into the dorsal hippocampus of male Wistar rats (200–250 g), immediately before ( n=9–20 animals/group) a 2 h period of forced restraint. After 24 h the animals were tested in the elevated plus maze. Non-stressed, control groups, received saline (SAL) or cycloheximide (CHX, n=6–12/group) and were tested 1 or 24 h later in the maze. Pre-stress microinjections of cycloheximide increased exploration of open arms in the elevated plus maze (percentage of entries, SAL=10.3±2.7, CHX 4 μg=24.5±4.6, CHX 8 μg=28.2±4.8, percentage of time spent, SAL=2.0±0.6, CHX 4 μg=8.4±2.3, CHX 8 μg=9.6±2.6, Duncan test, P<0.05). No drug effect was observed in non stressed animals. These results suggest that blockade of protein synthesis in the dorsal hippocampus during the restraint period may attenuate the behavioural consequences of stress.