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

Behav Pharmacol. 1997 Aug;8(4):331-8. doi: 10.1097/00008877-199708000-00006.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacology
  • Amygdala
  • Animals
  • Avoidance Learning
  • Benzazepines / pharmacology
  • Carbazoles*
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / drug effects
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Dopamine Agonists / pharmacology
  • Dopamine Antagonists / pharmacology
  • Hippocampus
  • Indoles / pharmacology
  • Male
  • Memory / drug effects*
  • Norepinephrine / pharmacology
  • Piperazines / pharmacology
  • Pyrroles / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, beta / drug effects
  • Receptors, Dopamine D1 / drug effects
  • Receptors, Serotonin / drug effects
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Signal Transduction / drug effects*
  • Time Factors
  • Timolol / pharmacology


  • Adrenergic alpha-Agonists
  • Adrenergic beta-Antagonists
  • Benzazepines
  • Carbazoles
  • Dopamine Agonists
  • Dopamine Antagonists
  • Indoles
  • Piperazines
  • Pyrroles
  • Receptors, Adrenergic, beta
  • Receptors, Dopamine D1
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • 1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine
  • Colforsin
  • KT 5720
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Timolol
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Norepinephrine