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Opposite effect of simple tetrahydroisoquinolines on amphetamine- and morphine-stimulated locomotor activity in mice

Opposite effect of simple tetrahydroisoquinolines on amphetamine- and morphine-stimulated locomotor activity in mice

Journal of Neural Transmission 108(5): 513-526

Endogenous tetrahydroisoquinolines, such as 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), were tested for their interaction with motor effects of amphetamine and morphine in C57BL/6 mice. TIQ binding to cortical adrenergic alpha1, alpha2 and beta receptors, striatal dopamine D1 and D2 receptors and cortical L-type calcium channels in the Wistar rat was also studied. Both compounds in high doses reduced the mouse locomotor activity, and in doses not affecting activity inhibited the motor stimulation induced by amphetamine, 2 or 3 mg/kg ip, but facilitated the hyperactivity induced by 10 mg/kg of morphine. TIQ did not displace ligands that are antagonists for several receptor sites (including D1 and D2 receptors), but displaced an agonist of alpha2-adrenoceptor, clonidine. It is proposed that TIQ and salsolinol specifically antagonize the agonistic conformation of dopamine receptor and that endogenous 1,2,3,4-tetrahydroisoquinolines may play a role of natural feedback regulators of the activity of dopaminergic system.

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Accession: 046870364

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PMID: 11459073

DOI: 10.1007/s007020170053

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