The effect of acute lithium administration on brain monoamine synthesis and the precursor amino acids tyrosine and tryptophan in brain and plasma in rats

Abstract

The effect of a single i.p. injection of lithium chloride on brain monoamine synthesis and tyrosine and tryptophan levels in brain and plasma in rats was studied. Acute lithium administration was found to decrease brain tyrosine levels, which most likely was due to decreased plasma tyrosine levels. Brain tryptophan levels were mainly unaffected whereas plasma tryptophan leves were slightly decreased at 8 hours after lithium administration. Brain catecholamine synthesis was decreased at 4 hours and increased at 48 hours after the injection of lithium. Brain 5-hydroxytryptamine (5-HT) synthesis was decreased at all time intervals after the injection of lithium. It is concluded that the effects of acute lithium administration on brain monoamine synthesis are not mainly due to its effect on brain tyrosine and tryptophan levels in rats. Furthermore acute lithium administration appears to affect 5-HT synthesis to a greater extent than it affects catecholamine synthesis.

Acute lithium administration selectively lowers tyrosine levels in serum and brain

“…High dose Li (7 mEq/kg IP) was previously reported to lower serum TYR (Berggren, 1985) in animals pretreated with NSD-1015 (Berggren, 1985), a potent inhibitor of hepatic tyrosine aminotransferase (Dyck, 1987). Whether Li affected other LNAAs had not been known.…”

“…While lithium (2–7 mEq/kg IP) had been previously reported to acutely lower striatal tissue TYR levels, those studies were conducted in animals pretreated with doses of NSD-1015 (Berggren, 1985; Berggren et al, 1980) that elevate brain TYR levels (Bongiovanni et al, 2008; Carlsson et al, 1972). Our data demonstrate that LiCl 2 (3 MEq/kg IP) selectively lowers brain TYR levels in otherwise untreated animals.…”

“…Part of the challenge is that Li exerts numerous effects in the central nervous system (Gould et al, 2004; McQuillin et al, 2007). These include anti-dopaminergic properties, evident in both pre-clinical (Beaulieu et al, 2004; Berggren, 1985; Berggren et al, 1980; O’Donnell and Gould, 2007; Otero Losada and Rubio, 1985) and clinical research studies (Sharma et al, 1989; van Kammen et al, 1985). Interestingly, some data have suggested that Li can lower brain tyrosine (TYR) availability (Berggren, 1985; Berggren et al, 1980).…”

“…These include anti-dopaminergic properties, evident in both pre-clinical (Beaulieu et al, 2004; Berggren, 1985; Berggren et al, 1980; O’Donnell and Gould, 2007; Otero Losada and Rubio, 1985) and clinical research studies (Sharma et al, 1989; van Kammen et al, 1985). Interestingly, some data have suggested that Li can lower brain tyrosine (TYR) availability (Berggren, 1985; Berggren et al, 1980). While a primary lowering of brain TYR can itself attenuate dopamine (DA)-mediated neurotransmission (Fernstrom and Fernstrom, 2007; Jaskiw and Bongiovanni, 2004; Jaskiw et al, 2008; Milner and Wurtman, 1986); the potential relationship between these Li effects has not been clarified.…”

“…One group reported that acutely administered Li lowered serum and brain levels of TYR as well as an index of DA synthesis (Berggren, 1985; Berggren et al, 1980); in those studies, however, Li was administered in conjunction with NSD-1015, a drug that affects brain TYR levels per se (Bongiovanni et al, 2008; Westerink and Wirix, 1983). In addition, possible Li effects on other large neutral amino acids (LNAAs) were not examined; the latter is important mechanistically, insofar as competition between serum LNAAs for blood–brain barrier transport is thought to be the major determinant of influx into and brain levels of LNAAs (Fernstrom and Faller, 1978; Kanai et al, 1998; Pardridge, 1998).…”