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The Preferential Effect of Simvastatin on Dopaminergic Agents Induced Behavioral Effect in Experimental Models of Depression
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| Author:
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DIGVIJAY RANA, UMESHKUMAR M. UPADHYAY, RAMESH K. GOYAL
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| Abstract:
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Objective: To study the effect of oral treatment of statins on dopamine D2 receptor modulators or other dopaminergic agents in acute models of depression.
Background – The role of dopamine and dopaminergic dysfunction has been established in the pathogenesis of depression. Various experimental and clinical studies have suggested a link between cholesterol and depression. Altered cholesterol level can produce alteration in neurotransmission, which in turn might affect the clinical efficacy of standard antidepressants.
Method: We have studied the effect of 30 days oral treatment of simvastatin on the immobility time at sub therapeutic doses of dopaminergic agents such as bromocriptine, haloperidol, bupropion and levodopa and compared such immobility time at higher doses of the same dopaminergic agents using the forced swim test (FST) and tail suspension test (TST) in mice.
Results- The anti immobility effect of simvastatin treated mice at the sub therapeutic dose of bromocriptine, bupropion and levodopa mimic the anti immobility effect to that of seen at the higher dose of bromocriptine, bupropion and levodopa in FST and TST. Simvastatin treated mice at the sub therapeutic dose of haloperidol did not show significant changes in the immobility time as compared to that of seen in simvastatin treated mice alone.
Conclusions: The present study suggests the possibility that statins may potentiate the antidepressant action of specific dopaminergic agents in depression and such facilitation of antidepressant action may be correlated with dopamine D2-like receptors in mediating the mevalonate pathway, which may have its potential implication in the treatment of depression.
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| Keyword:
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Cholesterol, Depression, Dopamine, Statins, Mice
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| DOI:
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