Late and prolonged post-training memory modulation in entorhinal and parietal cortex by drugs acting on the cAMP/protein kinase A signalling pathway.
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.
Ardenghi
P
P
Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul (U.F.R.G.S.), Porto Alegre, Brazil.
Barros
D
D
Izquierdo
L A
LA
Bevilaqua
L
L
Schröder
N
N
Quevedo
J
J
Rodrigues
C
C
Madruga
M
M
Medina
J H
JH
Izquierdo
I
I
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000679:Amygdala / Q000502:physiology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001552:Benzazepines / Q000494:pharmacology; D002227:Carbazoles; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018728:Entorhinal Cortex / Q000187:drug effects / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D010296:Parietal Lobe / Q000187:drug effects / Q000502:physiology*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*
D001552:Benzazepines; D002227:Carbazoles; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D007211:Indoles; D011758:Pyrroles; D015124:8-Bromo Cyclic Adenosine Monophosphate; C057416:KT 5720; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D017868:Cyclic AMP-Dependent Protein Kinases