These results demonstrated that lithium was neuroprotective against hypoxia only after chronic treatment and only in specific brain regions, and that CREB and BDNF might contribute to this effect.

We compared the potency of the interaction of three antipsychotic drugs, i.e. chlorpromazine (CPZ), haloperidol (Hal) and sulpiride (Sul), with the plasma membrane in the rat brain. CPZ loading (> or = 100 microM) dose-dependently increased both membrane permeability (assessed as [18F]2-fluoro-2-deoxy-D-glucose-6-phosphate release from brain slices) and membrane fluidity (assessed as the reduction in the plasma membrane anisotropy of 1,6-diphenyl-1,3,5-hexatriene). On the other hand, a higher concentration of Hal (1 mM) was required to observe these effects. However, Sul failed to change membrane permeability and fluidity even at a high concentration (1 mM). These results indicated the following ranking of the potency to interact with the membrane: CPZ>Hal>Sul. The difference among antipsychotic drugs in the potency to interact with the plasma membrane as revealed in the present study may be partly responsible for the difference among the drugs in the probability of inducing extrapyramidal side-effects such as parkinsonism and tardive dyskinesia.

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1-Methyl-4-phenylpyridinium (MPP(+)) was added directly to fresh rat brain slices and the dynamic changes in the cerebral glucose metabolic rate (CMRglc) were serially and two-dimensionally measured with [(18)F]2-fluoro-2-deoxy-D-glucose as a tracer. MPP(+) dose-dependently increased CMRglc, reflecting enhanced glycolysis compensating for the decrease in aerobic metabolism. While the CMRglc enhancement induced by MPP(+) (<10 microM) was restricted to the striatum, MPP(+) (>or=10 microM) induced a significant CMRglc enhancement in all brain regions. MPP(+) at high concentration (1 mM) eventually initiated rapid metabolic collapse, with failure to sustain anaerobic glycolysis.