Opposite Effects of Simple Tetrahydroisoquinolines on Amphetamine and Morphine-Stimulated Locomotor Activity in Mice

Abstract

Endogenous tetrahydroisoquinolines that may be formed in the brain spontaneously or in enzymatic reactions from dopamine or phenethylamine are generally regarded as neurotoxins that may be implicated in neurodegenerative diseases, particularly those specifically affecting the dopaminergic systems, as, e.g., Parkinson’s disease. Following our earlier results, demonstrating that chronic administration of tetrahydroisoquinoline (TIQ) and its derivative, salsolinol, may induce neurochemical changes compatible with experimental Parkinson’s disease, we presently investigated their acute effects on spontaneous locomotor activity and hypermotilities induced by amphetamine or morphine in C57/BL mice, and their propensity to interact with cortical noradrenaline α ₁, α ₂ and ß adrenoceptors, striatal dopamine D₁ and D₂ receptors, and cortical L-type calcium channels of the rat brain in vitro. Both TIQ and salsolinol reduced the spontaneous locomotor activity, and inhibited hyperactivity induced by amphetamine, 2 or 3mg/kg ip, when given at doses lower than those affecting the spontaneous locomotor activity. In contrast, both compounds facilitated the hypermotility induced by l0mg/kg ip of morphine. The effects of TIQ are not due to a direct receptor action, as the compound does not affect the specific radioligand binding to dopamine D₁ and D₂ receptors, nor adrenergic α ₁ and ß receptors, nor to L-type calcium channels in vitro. The only receptor action of the investigated tetrahydroisoquinolines was binding to adrenergic α ₂ receptors, and this action may be involved in the potentiation of morphine running fit.