Influence of SAMe on the modifications of brain polyamine levels in an animal model of depression.
The mechanism(s) of the antidepressant activity of S-adenosyl-L-methionine (SAMe) have not yet been elucidated. SAMe is essential for the synthesis of polyamines, which have a key role in protein synthesis, cell proliferation, and neuronal plasticity. On the other hand, accumulating data indicate that depression is associated with a reduction in regional brain volume and that antidepressants increase neurogenesis in defined brain regions and also influence neuronal plasticity. Here we show that in a validated rat model of depression (chronic unpredictable mild stress-induced anhedonia) there is a significant reduction of putrescine, spermidine and spermine in the hippocampus, and of only putrescine in the nucleus accumbens septi. SAMe, at a fully antidepressant dose (300 mg/kg i.m., daily for 7 days), completely restores the levels of putrescine in the nucleus accumbens, and restores in part the levels of both spermidine and spermine in the hippocampus. These results may suggest (i) a role for brain polyamines in depression and in reward processes, and (ii) that the antidepressant effect of SAMe may be due, at least in part, to a normalization of putrescine levels in the nucleus accumbens septi.
Genedani
S
S
Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia, Via G. Campi 287, 41100 Modena, Italy.
Saltini
S
S
Benelli
A
A
Filaferro
M
M
Bertolini
A
A
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D015317:Biogenic Polyamines / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D002908:Chronic Disease; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism*; D019422:Dietary Sucrose / Q000494:pharmacology; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D013312:Stress, Physiological / Q000188:drug therapy / Q000378:metabolism
D000928:Antidepressive Agents; D015317:Biogenic Polyamines; D019422:Dietary Sucrose; D012436:S-Adenosylmethionine