Chronic lithium chloride administration to rats elevates glucose metabolism in wide areas of brain, while potentiating negative effects on metabolism of dopamine D2-like receptor stimulation.

RATIONALE AND

OBJECTIVES

The regional cerebral metabolic rate for glucose (rCMRglc) can be imaged in vivo as a marker of brain functional activity. The effects of chronic lithium administration on baseline values of rCMRglc and values in response to administration of dopamine D2-like receptor agonists have not been examined in humans or rats. Knowing these effects may elucidate and localize the therapeutic action of lithium in bipolar disorder.

METHODS

In unanesthetized rats, we used the 2-deoxy-D-glucose (2-DG) technique to image the effects of a 6-week control diet or LiCl diet sufficient to produce a plasma lithium concentration therapeutically relevant to bipolar disorder, on rCMRglc at baseline and in response to the dopaminergic D2-like receptor agonist, quinpirole (1 mg/kg i.v.), or to i.v. saline.

RESULTS

Baseline rCMRglc was significantly elevated in 30 of 81 brain regions examined, in LiCl diet compared with control diet rats. Affected were visual and auditory structures, frontal cortex, amygdala, hippocampus, nucleus accumbens, caudate-putamen, interpeduncular nucleus, and substantia nigra. Acute quinpirole significantly decreased rCMRglc in four areas of the caudate-putamen in control diet rats, and in these and 19 additional brain areas in LiCl-fed rats.

CONCLUSIONS

In unanesthetized rats, chronic lithium administration widely upregulates baseline rCMRglc and potentiates the negative effects on rCMRglc of D2-like receptor stimulation. The baseline elevation may relate to lithium's reported ability to increase auditory and visual evoked responses in humans, whereas lithium's potentiation of quinpirole's negative effects on rCMRglc may be related to its therapeutic efficacy in bipolar disorder.