LATE AND PROLONGED POST-TRAINING MEMORY MODULATION IN ENTORHINAL AND PARIETAL CORTEX BY DRUGS ACTING ON THE CAMP PROTEIN KINASE-A SIGNALINGPATHWAY/

Rats implanted bilaterally with cannulae in the entorhinal or posterio r parietal cortex or in the amygdaloid nucleus were trained in one-tri al step-down inhibitory (passive) avoidance using a 0.3 mA footshock. At 0, 3, 6 or 9 h after training, they received localized 0.5 mu l inf usions into these areas of a vehicle, or of 8-Br-cAMP, forskolin (aden ylyl cyclase activator), KT5720 (protein kinase A inhibitor), SKF38393 (dopamine D-1 receptor agonist), SCH23390 (D-1 antagonist), norepinep hrine hydrochloride, timolol hydrochloride (beta blocker), 8-HO-DPAT ( 5-HT1A receptor agonist) or NAN-190 (5-HT1A antagonist) dissolved in 2 0% dimethylsulfoxide (DMSO) in saline (vehicle). Rats were tested for retention 24 h after training. 8-Br-cAMP, forskolin, SKF 38393 and nor epinephrine caused memory facilitation and KT5720, SCH23390, timolol a nd 8-HO-DPAT caused retrograde amnesia when given into the entorhinal cortex 0, 3 or 6 h but not 9 h after training. When given into the pos terior parietal cortex 0, 3 or 6 but not 9 h after training, KT5720 wa s amnestic. When given into this structure 3 or 6 h but not 0 or 9 h a fter training 8-Br-cAMP, forskolin and norepinephrine caused memory fa cilitation and KT5720, SCH23390 and timolol caused retrograde amnesia. All treatments given into the amygdala 0, 3 or 6 h after training wer e ineffective except for norepinephrine given at 0 h, which caused fac ilitation. The data point to a role of cAMP/protein kinase A-dependent mechanisms in memory formation in the entorhinal and parietal cortex, but not the amygdala, from 0 to 6 h after training, and to a strong m odulation of these mechanisms by dopaminergic D-1, beta-noradrenergic and 5-HT1A receptors. The lack of effect of NAN-190 but not 8-HO-DPAT in both cortical regions suggests that 5-HT1A receptors do not play a physiological role but can be activated pharmacologically. The fact th at SCH23390 was amnestic but SKF38393 had no effect when given into th e parietal cortex suggests that D-1 receptors may play a maintenance r ather than a stimulant role in this area.