Short- and long-term memory are differentially affected by metabolic inhibitors given into hippocampus and entorhinal cortex

Rats were implanted with cannulae in the CAI area of the dorsal hippocampus or in the entorhinal cortex and trained in one-trial step-down inhibitory avoidance, Two retention tests were carried out in each animal, one at 1.5 h to measure shortterm memory (STM) and another at 24 h to measure long-ter m memory (LTM). The purpose of the present study was to screen the effect o n STM of various drugs previously shown to affect LTM of this task when giv en posttraining at the same doses that were used here. The drugs and doses were the guanylyl cyclase inhibitor LY83583 (LY, 2.5 mu g), the inhibitor o f Tyr-protein kinase at low concentrations and of protein kinase G (PKG) at higher concentrations lavendustin A (LAV, 0.1 and 0.5 mu g), the PKG inhib itor KT5823 (2.0 mu g), the protein kinase C (PKC) inhibitor staurosporin ( STAU, 2.5 mu g), the inhibitor of calcium/ calmodulin protein kinase II (Ca MKII) KN62 (3.6 mu g), the protein kinase A (PKA) inhibitor KT5720 (0.5 mu g), and the mitogen-activated protein kinase kinase (MAPKK) inhibitor PD098 059 (PD, 0.05 mu g). PD was dissolved in saline; all the other drugs were d issolved in 20% dimethyl sulfoxide. In all cases the drugs affected LTM as had been described in previous papers. The drugs affected STM and LTM diffe rentially depending on the brain structure into which they were infused. ST M was inhibited by KT5720, LY, and PD given into CAL and by STAU and KT5720 given into the entorhinal cortex. PD given into the entorhinal cortex enha nced STM, LTM was inhibited by STAU, KN62, KT5720, KT5823, and LAV (0.5 mu g) given into CA1 and by STAU, KT5720, and PD given into the entorhinal cor tex. The results suggest that STM and LTM involve different physiological m echanisms but are to an extent Linked. STM appears to require PKA, guanylyl cyclase, and MAPKK activity in CAI;Ind PKA and PKC activity in the entorhi nal cortex; MAPKK seems to play an inhibitory role in STM in the entorhinal cortex, In contrast, LTM appears to require PKA and PKC activity in both s tructures, guanylyl cyclase, PKG, and CaMKII activity in CAI, and MAPKK act ivity in the entorhinal cortex, (C) 2000 Academic Press.