Late and prolonged post-training memory modulation in entorhinal and parietal cortex by drugs acting on the cAMP/protein kinase A signalling pathway

• Published in: Behavioural pharmacology Vol. 8; no. 8; p. 745
• Main Authors: Ardenghi, P, Barros, D, Izquierdo, L A, Bevilaqua, L, Schröder, N, Quevedo, J, Rodrigues, C, Madruga, M, Medina, J H, Izquierdo, I
• Format: Journal Article
• Language: English
• Published: England 01.12.1997
• Subjects: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - pharmacology; 8-Bromo Cyclic Adenosine Monophosphate - pharmacology; Amygdala - physiology; Animals; Avoidance Learning - drug effects; Avoidance Learning - physiology; Benzazepines - pharmacology; Carbazoles; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors; Cyclic AMP-Dependent Protein Kinases - physiology; Dopamine Agonists - pharmacology; Dopamine Antagonists - pharmacology; Entorhinal Cortex - drug effects; Entorhinal Cortex - physiology; Indoles - pharmacology; Male; Memory - drug effects; Parietal Lobe - drug effects; Parietal Lobe - physiology; Pyrroles - pharmacology; Rats; Rats, Wistar; Signal Transduction - drug effects
• ISSN: 0955-8810
• DOI: 10.1097/00008877-199712000-00010

Rats implanted bilaterally with cannulae in the entorhinal or posterior parietal cortex or in the amygdaloid nucleus were trained in one-trial 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 microliter infusions into these areas of a vehicle, or of 8-Br-cAMP, forskolin (adenylyl cyclase activator), KT5720 (protein kinase A inhibitor), SKF38393 (dopamine D1 receptor agonist), SCH23390 (D1 antagonist), norepinephrine hydrochloride, timolol hydrochloride (beta blocker), 8-HO-DPAT (5-HT1A receptor agonist) or NAN-190 (5-HT1A antagonist) dissolved in 20% dimethylsulfoxide (DMSO) in saline (vehicle). Rats were tested for retention 24 h after training. 8-Br-cAMP, forskolin, SKF 38393 and norepinephrine caused memory facilitation and KT5720, SCH23390, timolol and 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 posterior parietal cortex 0, 3 or 6 but not 9 h after training, KT5720 was amnestic. When given into this structure 3 or 6 h but not 0 or 9 h after training 8-Br-cAMP, forskolin and norepinephrine caused memory facilitation and KT5720, SCH23390 and timolol caused retrograde amnesia. All treatments given into the amygdala 0, 3 or 6 h after training were ineffective except for norepinephrine given at 0 h, which caused facilitation. 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 modulation of these mechanisms by dopaminergic D1, 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 that SCH23390 was amnestic but SKF38393 had no effect when given into the parietal cortex suggests that D1 receptors may play a maintenance rather than a stimulant role in this area.