Zinc deficiency alters responsiveness to antidepressant drugs in mice.
BACKGROUND
There is some evidence coming from preclinical and clinical studies suggesting a relationship between dietary zinc intake and depressive symptoms. The aim of the study was to determine whether zinc deficiency alters the response to antidepressants with a different mechanism of action. We examine also whether these changes are related to activity of the hypothalamic-pituitary-adrenal HPA axis.


METHODS
Male CD-1 mice were assigned to groups according to diet and antidepressant administration. To evaluate animal behavior, the immobility time in the forced swim test (FST) and locomotor activity were measured. To determine serum zinc levels the flame atomic absorption spectroscopy (FAAS) was used. The serum corticosterone was determined by radioimmunoassay (RIA).


RESULTS
Antidepressants administered to zinc-deprived mice induced an altered response in the FST when compared to animals fed with an adequate diet. There were no changes in locomotor activity. Animals subjected to a zinc-deficient diet showed a significant reduction in serum zinc levels, which was normalized by antidepressant treatment. An increase in serum corticosterone concentrations in mice fed with a zinc-deficient diet and treated with antidepressants was observed, so it can be concluded that reduced levels of zinc contribute hyperactivation of the HPA axis.


CONCLUSIONS
The results of this study suggest that a diet with a reduced zinc level alters antidepressant action, which is associated with a reduction in the serum zinc level and rise in the corticosterone level. The results of this study may indicate the involvement of zinc deficiency in the pathogenesis of depression.
Department of Biochemical Toxicology, Jagiellonian University Medical College, Kraków, Poland. katarzyna.mlyniec@uj.edu.pl
Katarzyna
K
Młyniec
Bogusława
B
Budziszewska
Witold
W
Reczyński
Urszula
U
Doboszewska
Andrzej
A
Pilc
Gabriel
G
Nowak
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000097:blood / Q000188:drug therapy*; D004032:Diet; D004195:Disease Models, Animal; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects; D013550:Swimming; D015032:Zinc / Q000097:blood* / Q000172:deficiency*
D000928:Antidepressive Agents; D015032:Zinc; D003345:Corticosterone