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Comparison of tyrosine hydroxylase and dopamine-Β-hydroxylase inhibition with the effects of various 6-hydroxydopamine treatments on d-amphetamine induced motor activity

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Abstract

The significance of central noradrenergic and dopaminergic neural systems for the locomotor stimulant effects of d-amphetamine were investigated in rats with depletions of norepinephrine, dopamine, or both catecholamines produced by treatment with either reserpine, L-α-methyl-tyrosine (α-MPT), 6-hydroxydopamine (6-OHDA), or the dopamine-Β-hydroxylase inhibitor 1-phenyl-3-(2-thiazolyl)-2-thiourea (U-14,624). In animals pretreated with reserpine, amphetamine-stimulated locomotor activity was blocked by Β-MPT but not by U-14,624 when amphetamine was given l h after these catecholamine synthesis inhibitors. In rats with chronic depletions of brain norepinephrine, dopamine, or both catecholamines produced by different 6-OHDA treatments, both amphetamine-stimulated motor activity and stereotyped behavior were antagonized by treatments reducing dopamine or both catecholamines but not in animals in which brain norepinephrine was reduced. Results are consistent with the view that the locomotor stimulation and stereotyped behaviors produced by d-amphetamine are dependent upon functional dopaminergic neural systems in brain.

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  1. Departments of Pharmacology and Psychiatry, Biological Sciences Research Center, Child Development Institute, University of North Carolina School of Medicine, Chapel Hill, North Carolina

    Alan S. Hollister, George R. Breese & Barrett R. Cooper

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  1. Alan S. Hollister
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  2. George R. Breese
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  3. Barrett R. Cooper
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Hollister, A.S., Breese, G.R. & Cooper, B.R. Comparison of tyrosine hydroxylase and dopamine-Β-hydroxylase inhibition with the effects of various 6-hydroxydopamine treatments on d-amphetamine induced motor activity. Psychopharmacologia 36, 1–16 (1974). https://doi.org/10.1007/BF00441377

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