title: Drugs acting upon the cyclic adenosine monophosphate/protein kinase A signalling pathway modulate memory consolidation when given late after training into rat hippocampus but not amygdala.
abstract: Rats implanted bilaterally with cannulae in the CA1 region of the dorsal hippocampus or in the amygdala were trained in one-trial step-down inhibitory (passive) avoidance using a 0.4 mA footshock. At various times after training (0, 1.5, 3, 6 or 9 h for animals implanted in the hippocampus; 0 or 3 h for those implanted in the amygdala), they received infusions of 8-Br-cAMP (cyclic adenosine monophosphate) (1.25 micrograms/side), SKF38393 (7.5 micrograms/side), SCH23390 (0.5 microgram/side), norepinephrine ClH (0.3 microgram/side), timolol ClH (0.3 microgram/side), 8-HO-DPAT (2.5 micrograms/side), NAN-190 (2.5 micrograms/side), forskolin (0.5 microgram/side) or KT5720 (0.5 microgram/side). Rats were tested for retention 24 h after training. SKF38393 is an agonist and SCH23390 an antagonist at dopamine D1 receptors, timolol is a beta-adrenoceptor antagonist, 8-HO-DPAT is an agonist and NAN-190 an antagonist at 5HT1A receptors, forskolin enhances adenylyl cyclase, and KT5720 inhibits protein kinase A. When given into the hippocampus 0 h post-training, norepinephrine enhanced memory and KT5720 was amnestic. When given 1.5 h after training, all treatments were ineffective. When given 3 or 6 h post-training, 8-Br-cAMP, forskolin, SKF 38393, noradrenaline and NAN-190 caused memory facilitation, and KT5720, SCH23390, timolol and 8-HO-DPAT caused retrograde amnesia. At 9 h from training, all treatments were again ineffective. When given into the amygdala 0 or 3 h post-training all treatments were ineffective, except for noradrenaline at 0 h, which caused retrograde facilitation. The data agree with the suggestion that in the hippocampus, but not the amygdala, a cAMP/protein kinase A pathway is involved in memory consolidation at 3 and 6 h from training, and that this is regulated by D1, beta, and 5HT1A receptors. This correlates with a previous report of increased cAMP levels, protein kinase A activity and P-CREB levels at 3-6 h from training in rat hippocampus in this task. This may be taken to suggest that the hippocampus, but not the amygdala, is involved in the long-term storage of step-down inhibitory avoidance in the rat.
authors.affiliation: Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul (U.F.R.G.S.), Porto Alegre, RS, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Bevilaqua
authors.forename: P
authors.initials: P
authors.lastname: Ardenghi
authors.forename: N
authors.initials: N
authors.lastname: Schröder
authors.forename: E
authors.initials: E
authors.lastname: Bromberg
authors.forename: P K
authors.initials: PK
authors.lastname: Schmitz
authors.forename: E
authors.initials: E
authors.lastname: Schaeffer
authors.forename: J
authors.initials: J
authors.lastname: Quevedo
authors.forename: M
authors.initials: M
authors.lastname: Bianchin
authors.forename: R
authors.initials: R
authors.lastname: Walz
authors.forename: J H
authors.initials: JH
authors.lastname: Medina
authors.forename: I
authors.initials: I
authors.lastname: Izquierdo
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000679:Amygdala; D000818:Animals; D001362:Avoidance Learning; D001552:Benzazepines / Q000494:pharmacology; D002227:Carbazoles; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006624:Hippocampus; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D013999:Timolol / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D002227:Carbazoles; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D007211:Indoles; D010879:Piperazines; D011758:Pyrroles; D011943:Receptors, Adrenergic, beta; D017447:Receptors, Dopamine D1; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D005576:Colforsin; C057416:KT 5720; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D013999:Timolol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D009638:Norepinephrine