Protein kinase C activation and anti-amnesic effect of acetyl-L-carnitine: in vitro and in vivo studies.
Drugs belonging to different chemical classes having the ability to improve behavioral performance in animal learning and memory tests may share the common ability to stimulate protein kinase C activity in rat brain cortex. In vitro acetyl-L-carnitine (100 nM) promoted in rat brain cortex slices a significant increase in particulate activity associated with lower soluble protein kinase C activity and produced a direct stimulation of the enzyme in both the cortex and hippocampus. In vivo a significant increase in particulate protein kinase C activity was observed in the group of rats treated with 60 mg/kg acetyl-L-carnitine, a dose shown to be effective in improving the cognitive deficits induced by scopolamine in the Morris maze test. The results suggest that acetyl-L-carnitine increases particulate protein kinase C activity in the cortex both in vitro and in vivo. This effect in the in vivo experiments seems to be observed only with doses that are effective in improving the performance of rats in a spatial learning task.
Pascale
A
A
Institute of Pharmacological Sciences, University of Milan, Italy.
Milano
S
S
Corsico
N
N
Lucchi
L
L
Battaini
F
F
Martelli
E A
EA
Trabucchi
M
M
Govoni
S
S
D000108:Acetylcarnitine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D003072:Cognition Disorders / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000008:administration & dosage / Q000633:toxicity
D000108:Acetylcarnitine; D012601:Scopolamine; D011493:Protein Kinase C