adenosine-3--5--cyclic-phosphorothioate and Amnesia--Anterograde

Rats were bilaterally implanted with indwelling cannulae in the CA1 region of the dorsal hippocampus. After recovery from surgery, they were trained in a one-trial, step-down inhibitory avoidance task using a 0.5 mA foot shock. The animals received intrahippocampal infusions of either vehicle or anandamide (100 microM, 0.5 microl/side) 30 min before training. Then, either immediately post-training or 3 h later, they received infusions of saline, noradrenaline (0.5 microg/side), SKF 38393 (1.5 microg/side), oxotremorine (0.6 microg/side) or Sp-cAMPs (0.5 microg/side) also in the hippocampus. All animals were tested for retention 24-h post-training. Anandamide produced anterograde amnesia. Immediate, but not delayed, post-training treatment with Sp-cAMPs and noradrenaline reversed this effect. SKF 38393 and oxotremorine had no influence on the amnesia caused by anandamide either when given immediately or 3 h after training. The results suggest that the amnesic effect of anandamide is related to the known noradrenergic regulation of cAMP-dependent protein kinase (PKA) activity previously described in the hippocampus immediately after avoidance training, which is crucial to long-term memory (LTM) formation.

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Amnesia, Anterograde; Animals; Arachidonic Acids; Avoidance Learning; Behavior, Animal; Calcium Channel Blockers; Chi-Square Distribution; Cyclic AMP; Dopamine Agonists; Dose-Response Relationship, Drug; Endocannabinoids; Enzyme Inhibitors; Hippocampus; Memory; Morphine; Muscarinic Agonists; Narcotics; Norepinephrine; Oxotremorine; Polyunsaturated Alkamides; Rats; Rats, Wistar; Reaction Time; Thionucleotides