Influence of S-adenosyl-L-methionine
on chronic mild stress-induced
anhedonia in castrated rats
by
Benelli A, Filaferro M, Bertolini A, Genedani S
Department of Biomedical Sciences,
University of Modena and Reggio Emilia,
Italy.
benelli.augusta@unimo.it
Br J Pharmacol 1999 Jun; 127(3):645-54
ABSTRACT
1. S-adenosyl-L-methionine (SAMe) is the most important methyl donor in the
brain and is essential for polyamine synthesis. Methyl group deficiency in the
brain has been implicated in depression; on the other hand, polyamines enhance
phosphorylation processes, and phosphorylation of functional proteins in neurons
in involved in the therapeutic mechanisms of antidepressants. 2. The effect of
SAMe in an animal model of 'depression', the chronic mild stress-induced
anhedonia, was studied using long-term castrated male and female Lister hooded
rats. 3. Chronic daily exposure to an unpredictable sequence of mild stressors
produced, within 3 weeks, a significant reduction of the consumption of a
sucrose solution. SAMe (100, 200 or 300 mg kg-1 daily i.m.) while having no
influence on sucrose intake in non-stressed animals, dose-dependently reinstated
sucrose consumption within the first week of treatment, both in male and in
female stressed rats. Imipramine (10 mg kg-1 daily i.p.) produced a similar
effect after a 3 week treatment. 4. Similarly, a palatable food reward-induced
place preference conditioning was developed in SAMe (200 or 300 mg kg-1 daily
i.m.)--and in imipramine (10 mg kg-1 daily i.p.)--treated chronically stressed
animals (males and females), whilst it could not be obtained in vehicle-treated
rats. 5. Moreover, the same doses of SAMe (but not of imipramine) restored the
exploratory activity and curiosity for the environment (rearing), in the
open-field test. 6. While imipramine caused a blockade of the growth throughout
the treatment, SAMe produced only a transient growth arrest during the first
week of treatment. 7. These results show that SAMe reverses an experimental
condition of 'depression-like' behaviour in rats, the effect being more rapid
and complete than that of imipramine, and without apparent side effects.
LHPA
SAMe
Cannabis
Hypericum
Anhedonia
SAMe mania
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