Monoamines and their metabolites in Huntington's disease brain: Evidence for decreased catechol-O-methyltransferase activity

Abstract

Alterations in dopaminergic neurotransmission in the degenerating neostriatum have been implicated in the generation of choreic movements in Huntington's disease (HD), Arguments cited in support are the contrast with parkinsonian hypokinesia and the effects of dopamine (DA) agonists and antagonists in, respectively, exacerbating and suppressing involuntary movements (Klawans et al 1972). Striatal concentrations of DA have generally been reported to be normal (Bird and Iversen 1974; Melamed et al 1982; Reynolds and Garrett 1986; Beal et al 1990), although elevated levels were found in single studies in the caudate (Spokes 1980) or putamen (Melamed et al 1982), and a decreased level was found by Kish et al (1987) in the caudal eaudate. Physiologically more important, however, may be the relative concentrations of DA and its metabolites, as these may indicate local dopamine turnover. The literature on DA metabolites in HD brains is scarce. Normal homovanillic acid (HVA) concentrations were reported by Melamed et al (1982) and Beal et al (1990), but Reynolds and Garrett (1986) found significantly low levels. As with DA itself, the concentration of HVA was found by Kish et al (1987) to be decreased in the caudal caudate. Only Beal et al (1990) studied 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methox_vtyramine (MET); their levels were not significantly abnormal in the putamen, although the mean concentration in HD was 119% of control for DOPAC and 81% for MeT. Naudon et al (1992) recently reported that, 2 days after a kainic acid (KA) lesion of rat striatum, there are elevated levels of DOPAC and HVA but markedly reduced levels of MeT. They interpreted their data as indicating a loss of cateeholamine-Ometh'~l transferase (COMT) in the lesioned striatum. A substantial decrease in COMT acti.vi:y in KA-lesioned striatum was