Effect of low-dose lithium administration and subsequent withdrawal on biogenic amines in rat brain.

1 The effects of low-dose lithium administration (2 mEq/kg, daily) and its subsequent withdrawal have been examined with reference to changes in biogenic amine systems in several discrete regions of rat brain. 2 Increased levels of striatal tyrosine and midbrain tryptophan were found following lithium administration together with slight decreases in striatal tyrosine hydroxylase and midbrain tryptophan hydroxylase activities. Withdrawal resulted in a decrease in tyrosine content with increased tyrosine hydroxylase activity, whilst tryptophan levels and tryptophan hydroxylase activity were increased. 3 Lithium treatment and withdrawal resulted in altered levels of noradrenaline and dopamine, these changes being regionally variable. 3-Methoxy-4-hydroxyphenylglycol content was depressed in both treated and withdrawal rats as were 3,4-dihydroxyphenylacetic acid levels. Homovanillic acid decreased as a result of lithium treatment, but was greatly elevated in the withdrawal group. 4 5-Hydroxytryptamine content decreased in some brain regions following lithium treatment with return towards control values in withdrawal rats. 5-Hydroxyindoleacetic acid levels also displayed a regional variation as a result of lithium treatment and withdrawal. 5 The implications of these observations in elucidating the pharmacological effect of lithium treatment and its subsequent withdrawal are discussed.