Reversible inactivation of the medial septal area impairs consolidation but not retrieval of passive avoidance learning in rats.

Involvement of the medial septal area (MSA) in consolidation and retrieval of passive avoidance response (PAR) was investigated with functional suppression of this area by tetrodotoxin (TTX). Rats carrying a chronically implanted cannula aimed at the MSA were trained on a step-through passive avoidance task and received intraseptal injection of 5 ng TTX dissolved in 1 microliter saline 5, 90 and 360 min after the acquisition trial or 60 min before the retrieval test. TTX injected 5 and 90 min after the acquisition trial significantly reduced avoidance of the dark compartment in comparison with the control group injected with saline. PAR was not impaired by septal TTX injected 360 min after acquisition or 60 min before the retrieval test. Step-through latency of naive rats was not affected by septal blockade. The results indicate that the MSA contributes to PAR consolidation at least 90 min after acquisition but its involvement in PAR retrieval is unlikely. It is concluded that functional ablation of the MSA may disrupt integrity of subcortical circuits participating in PAR learning.

Tolerance to ketamine-induced blockade of cortical spreading depression transfers to MK-801 but not to AP5 in rats.

Tolerance to ketamine (KET) induced blockade of cortical spreading depression (CSD) was investigated in 31 rats anesthetized with pentobarbital. CSD was elicited by injection of 1 microl of 5% KCl into cortex at 15 min intervals and monitored by recording the accompanying slow potential waves. After control recording, five injections of KET (50 mg/kg) were applied at 75 min intervals. The first KET injection elicited CSD blockade lasting for 30-45 min at the near and for 60-75 min at the far electrode. The CSD blocking effect of subsequent injections gradually declined and was not recognizable after the fifth KET injection. MK-801 (2.5 mg/kg) injected to rats with fully developed KET tolerance 30 min after the last KET dose, failed to block CSD. Without KET pretreatment the same dosage of MK-801 induced CSD blockade lasting more than 1 h. KET tolerance did not prevent local CSD blockade in a cortical area superfused with 10(-3) mol/l AP5. It is concluded that repeated applications of KET may induce some conformational changes at binding site(s) in the N-methyl-D-aspartate (NMDA) controlled channels shared by both KET and MK-801.