Effects of psychoactive drugs on cellular bioenergetic pathways

Abstract

Objectives

To investigate the actions of lithium, valproate, lamotrigine and quetiapine on bioenergetic pathways in cultured NT2-N neuronal-like cells and C8-B4 microglial cells.

Methods

NT2-N and C8-B4 cells were cultured and treated with lithium (2.5 mM), valproate (0.5 mM), quetiapine (0.05 mM) or lamotrigine (0.05 mM) for 24 hours. Gene expression and the mitochondrial bioenergetic profile were measured in both cell lines.

Results

In NT2-N cells, valproate increased oxidative phosphorylation (OXPHOS) gene expression, mitochondrial uncoupling and maximal respiratory capacity, while quetiapine decreased OXPHOS gene expression and respiration linked to ATP turnover, as well as decreasing the expression of genes in the citric acid cycle. Lamotrigine decreased OXPHOS gene expression but had no effect on respiration, while lithium reduced the expression of genes in the citric acid cycle. In C8-B4 cells, valproate and lithium increased OXPHOS gene expression, and valproate increased basal respiratory rate and maximal and spare respiratory capacities. In contrast, quetiapine significantly reduced basal respiratory rate and maximal and spare respiratory capacities.

Conclusions

Overall our data suggest that some drugs used to treat neuropsychiatric and affective disorders have actions on a range of cellular bioenergetic processes, which could impact their effects in patients.

Keywords:

• Mitochondria
• bioenergetic
• psychoactive drugs
• neurons
• microglia

Acknowledgement

CB is supported by an Alfred Deakin Postdoctoral Research Fellowship. MB is supported by a NHMRC Senior Principal Research Fellowship 1059660 and 1156072.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Health and Medical Research Council (NHMRC) Project Grant [APP1078928].