Differential Regional Effects of Methamphetamine on the Activities of Tryptophan and Tyrosine Hydroxylase

• Published in: Journal of neurochemistry Vol. 72; no. 2; pp. 661 - 668
• Main Authors: Haughey, Heather M., Fleckenstein, Annette E., Hanson, Glen R.
• Format: Journal Article
• Language: English
• Published: Oxford UK Blackwell Science Ltd 01.02.1999; Blackwell
• Subjects: Animals; Biological and medical sciences; Brain - drug effects; Brain - enzymology; Catecholaminergic system; Caudate nucleus; Caudate Nucleus - drug effects; Caudate Nucleus - enzymology; Central Nervous System Stimulants - pharmacology; Dose-Response Relationship, Drug; Enzyme Activation - drug effects; Globus Pallidus - drug effects; Globus Pallidus - enzymology; Male; Medical sciences; Methamphetamine; Methamphetamine - pharmacology; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Nucleus accumbens; Nucleus Accumbens - drug effects; Nucleus Accumbens - enzymology; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Striatum; Tryptophan - metabolism; Tryptophan hydroxylase; Tyrosine 3-Monooxygenase - metabolism; Tyrosine hydroxylase; Amphetamine derivatives; Intraperitoneal administration; CNS stimulant; Rat; Enzyme; Rodentia; Central nervous system; Metamfetamine; Basal ganglion; Corpus striatum; Sympathomimetic; Tyrosine 3-monooxygenase; Nucleus accumbens; Vertebrata; Mammalia; Caudate nucleus; Enzymatic activity; Tryptophan 5-monooxygenase; Animal; Oxidoreductases; Brain (vertebrata)
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1999.0720661.x

: Administration of high doses of methamphetamine (METH) produces both short‐ and long‐term enzymatic deficits in central monoaminergic systems. To determine whether a correlative relationship exists between these acute and long‐term consequences of METH treatment, in the present study we examined the regional effects of METH on tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activities in various regions of the caudate nucleus, nucleus accumbens, and globus pallidus. A single METH administration decreased TPH activity 1 h after treatment in the globus pallidus, in the nucleus accumbens, and throughout the caudate ; in the anterior caudate, the ventral‐medial was more affected than the dorsal‐lateral region. In contrast, TH activity was not decreased in either the caudate or the globus pallidus after a single METH administration ; however, it was altered in the nucleus accumbens. Seven days after multiple METH administrations, TH and TPH activities were decreased in most caudate regions but not in the nucleus accumbens or globus pallidus. These data demonstrate that (1) the effects of METH on TPH and TH vary regionally ; and (2) the short‐term and long‐term regional responses of TPH to METH in the caudate and globus pallidus correlated. In contrast, METH‐induced acute TH responses did not predict the long‐term changes in TH activity.