In earlier studies the
tetrahydroisoquinoline derivative N-methyl-
norsalsolinol (2-MDTIQ) was discovered in lumbar cerebrospinal fluid and brain of patients with
Parkinson's disease. To establish whether
2-MDTIQ is toxic to the dopaminergic system,
2-MDTIQ or
6-hydroxydopamine (6-OHDA) were stereotactically injected into the left medial forebrain bundle, and rotational behaviour and neurochemical changes were measured in female Wistar rats. Three weeks after lesioning rotational behaviour was assessed after administration of S(+)-
amphetamine (5 mg/kg) and
apomorphine (0.1 mg/kg). As expected, after
6-OHDA lesions S(+)-
amphetamine as well as
apomorphine markedly induced rotations ipsiversive or contraversive, respectively, to the lesion, and
dopamine and
3,4-dihydroxyphenylacetic acid (
DOPAC) levels of the ipsilateral caudate-putamen and accumbens nucleus decreased. Although a decline in the
dopamine/
DOPAC ratio indicated an enhanced
dopamine turnover, striatal
monoamine oxidase (
MAO) activity remained unchanged when tested in vitro. After a
2-MDTIQ lesion S(+)-
amphetamine also caused animals to rotate strongly, ipsiversive to the lesion, but there was no response to
apomorphine administration. This
2-MDTIQ effect was not due to a reduction in
dopamine metabolism of the ipsilateral caudate-putamen or mesencephalic structures, or, for example, a partial neurodegeneration of dopaminergic neurons, since
dopamine metabolites levels and
MAO activity were nearly unchanged. Thus, we suggest that
2-MDTIQ interacts with the effect of S(+)-
amphetamine and probably leads to an insensitivity of the
dopamine uptake/transporter system to S(+)-
amphetamine in dopaminergic nigrostriatal neurons. An effect of
2-MDTIQ on presynaptic membranes of dopaminergic synaptosomes has never been reported, but will be an objective of our further studies.