Effect of acute and chronic administration of 1,2,3,4-tetrahydroisoquinoline on muscle tone, metabolism of dopamine pn the striatum and tyrosine hydroxylase immunocytochemistry in the substantia nigra, in rats

The effects of acute and chronic administration of 1,2,3,4-tetrahydroisoqui noline, an endogenous substance suspected of producing parkinsonism in huma ns, on the muscle tone and metabolism of dopamine in the striatum, and on t he number of tyrosine hydroxylase-immunoreactive cells in the substantia ni gra were investigated in rats. Muscle tone was examined using a combined me chanomyographic and electromyographic method which measured simultaneously the muscle resistance of the rat's hind foot to passive extension and flexi on in the ankle joint and electromyographic activity of the antagonistic mu scles of that joint: gastrocnemius and tibialis anterior. 1,2,3,4-Tetrahydr oisoquinoline administered at doses of 50 and 100 mg/kg intraperitoneally f or 19 days increased muscle resistance 1 h after the first injection (acute treatment), I h after the last injection (chronic treatment) and three day s after compound withdrawal. Rigidity observed on the third day of 1,2,3,4- tetrahydroisoquinoline withdrawal was accompanied by an increased tonic (re sting) electromyographic activity of the gastrocnemius and tibialis anterio r muscles. At the same time, a significant reduction in the number of tyros ine hydroxylase-immunoreactive neurons in the substantia nigra and a decrea se in the dopamine level in the striatum were also found. A declining numbe r of tyrosine hydroxylase-immunoreactive neurons in the whole substantia ni gra showed a significant negative correlation with the enhanced muscle resi stance, as well as with the tonic electromyographic activity recorded at re st, i.e. before the start of movements, from the gastrocnemius and tibialis anterior muscles. Our results suggest that 1,2,3,4-tetrahydroisoquinoline may be one of the e ndogenous substances involved in the progress of Parkinson's disease. (C) 1 999 IBRO. Published by Elsevier Science Ltd.