title: Norepinephrine does not contribute to methamphetamine-induced changes in hippocampal serotonergic system.
abstract: The purpose of this study was to determine whether norepinephrine (NE) mediated the reduction in the activity of tryptophan hydroxylase (TPH) in the hippocampus and other serotonergic changes, induced by a single or multiple administrations of methamphetamine. The NE in the hippocampus was depleted by injecting rats with DSP4 intraperitoneally, 10 days prior to administration of methamphetamine. A single administration of methamphetamine (15 mg/kg) reduced the activity of TPH to 40% of control after 3 hr. A 90 to 98% reduction in the concentration of NE in the hippocampus, failed to alter this methamphetamine-induced response. The reduction in serotonin (5-HT) in the hippocampus induced by methamphetamine, was not altered by the treatment with DSP4. These observations were confirmed by a lack of effect on methamphetamine-induced changes in 5-HT and TPH after inhibition of the synthesis of NE with U-14,624. The pretreatment with DSP4 also failed to block the decline in activity of TPH in the hippocampus or concentrations of 5-HT measured 18 hr after the last of 4 doses of methamphetamine (15 mg/kg, s.c.). The results presented in this study indicate that NE is not involved in the response of the serotonergic system to methamphetamine.
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112.
authors.forename: M
authors.initials: M
authors.lastname: Johnson
authors.forename: G R
authors.initials: GR
authors.lastname: Hanson
authors.forename: J W
authors.initials: JW
authors.lastname: Gibb
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D010668:Phenylthiazolylthiourea / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D013566:Sympathomimetics / Q000494:pharmacology; D014365:Tryptophan Hydroxylase / Q000378:metabolism
chemical_list: D001596:Benzylamines; D013566:Sympathomimetics; D010668:Phenylthiazolylthiourea; D012701:Serotonin; D008694:Methamphetamine; D006897:Hydroxyindoleacetic Acid; D014365:Tryptophan Hydroxylase; C012102:DSP 4; D009638:Norepinephrine