Transitory effects of intracerebral administration of protein synthesis inhibitors on rat's spontaneous behavior.

Abstract

In order to evaluate whether the effects of the local administration of protein synthesis inhibitors are transient or permanent, small volumes of cycloheximide, 2-deoxy-d-galactose, tetrodotoxin, and saline solution were stereotaxically administered in the amygdala, substantia nigra, and nucleus basalis magnocellularis of naive male adult Wistar rats. Three spontaneous activities (feeding, drinking, locomotion) were continuously recorded. 12 groups of animals were housed in activity cages for 6 consecutive days with a light/dark schedule (LD 12:12). The active compounds at doses sufficient to cause only limited effects were administered at the beginning of the light period of the fourth day. During the initial three days spontaneous activities remained constant, following the normal circadian distribution of rodents. Cycloheximide and tetrodotoxin administrations were followed by transient site-specific and activity-specific changes, which occurred only during the fourth and fifth day. The results show that protein synthesis inhibitors can be locally administered into the CNS at doses affecting only limited subcortical structures. The observed modifications of the three spontaneous activities were all transient and were always followed by complete recovery within 48 hours, thus confirming previous biochemical data. Therefore, the local injection of protein synthesis inhibitors, like tetrodotoxin, lidocaine or other compounds, can be employed to induce transient functional effects on well delimited brain structures in order to study the time-course of the mechanism of mnemonic trace formation.