Methamphetamine (MA), a widely used drug of abuse, produces oxidative damage of nigrostriatal dopaminergic terminals. We examined the effect of subtype-selective ligands of metabotropic glutamate (mGlu) receptors on MA neurotoxicity in mice. MA (5 mg/kg, i.p.; injected three times, every 2 hr) induced, 5 d later, a substantial degeneration of striatal dopaminergic terminals associated with reactive gliosis. MA toxicity was primarily attenuated by the coinjection of the noncompetitive mGlu5 receptor antagonists 2-methyl-6-(phenylethynyl)pyridine and (E)-2-methyl-6-styrylpyridine both at 10 mg/kg, i.p.). In contrast, the mGlu1 receptor antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (10 mg/kg, i.p.), and the mGlu2/3 receptor agonist (-)-2-oxa-4-aminocyclo[3.1.0]hexane-4,6-dicarboxylic acid (1 mg/kg, i.p.), failed to affect MA toxicity. mGlu5 receptor antagonists reduced the production of reactive oxygen species but did not reduce the acute stimulation of dopamine release induced by MA both in striatal synaptosomes and in the striatum of freely moving mice. We conclude that endogenous activation of mGlu5 receptors enables the development of MA neurotoxicity and that mGlu5 receptor antagonists are neuroprotective without interfering with the primary mechanism of action of MA.

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ABSTRACT3 H]spiperone to Chinese hamster ovary-transfected D 3 receptors when radioligands were used at 0.2 and 0.5 nM, respectively. However, even at high concentrations (5 M), SB269,652 only submaximally inhibited the specific binding of these radioligands when they were employed at 10-fold higher concentrations. By analogy, although SB269,652 potently blocked D 3 receptor-mediated activation of G␣ i3 and phosphorylation of extracellular-signal-regulated kinase (ERK)1/2, when concentrations of dopamine were increased by 10-fold, from 1 M to 10 M, SB269,652 only submaximally inhibited dopamine-induced stimulation of G␣ i3 . SB269,652 (up to 10 M) only weakly and partially (by approximately 20 -30%) inhibited radioligand binding to D 2 receptors. Likewise, SB269,652 only submaximally suppressed D 2 receptor-mediated stimulation of G␣ i3 and G␣ qi5 (detected with the aequorin assay) and phosphorylation of ERK1/2 and Akt. Furthermore, SB269,652 only partially (35%) inhibited the dopamine-induced recruitment of ␤-arrestin2 to D 2 receptors. Finally, Schild analysis using G␣ i3 assays, and studies of radioligand association and dissociation kinetics, supported allosteric actions of SB269,652 at D 3 and D 2 receptors.

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This study explores the effect of continuous exposure to bright light on neuromelanin formation and dopamine neuron survival in the substantia nigra. Twenty-one days after birth, Sprague–Dawley albino rats were divided into groups and raised under different conditions of light exposure. At the end of the irradiation period, rats were sacrificed and assayed for neuromelanin formation and number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra. The rats exposed to bright light for 20 days or 90 days showed a relatively greater number of neuromelanin-positive neurons. Surprisingly, TH-positive neurons decreased progressively in the substantia nigra reaching a significant 29% reduction after 90 days of continuous bright light exposure. This decrease was paralleled by a diminution of dopamine and its metabolite in the striatum. Remarkably, in preliminary analysis that accounted for population density, the age and race adjusted Parkinson's disease prevalence significantly correlated with average satellite-observed sky light pollution.

The taxonomic position of the monotypic genus Lydomorphus Fairmaire 1882 is clarified. The examination of the type series of L. cinammomeus Fairmaire 1882 indicated that the large genus Cylindrothorax Escherich 1896 is a junior synonym of Lydomorphus (n. syn.); consequently new combinations for 73 species are proposed. The male syntype is designated as lectotype of L. cinammomeus. The female syntype belongs to L. angusticollis (Haag-Rutenberg 1880), the closest relative of L. cinammomeus. L. cinammomeus is redescribed and figured, and Cylindrothorax csikii Kaszab 1955 is synonymized with it (n. syn.). Two new subgenera, Pardolydus [including only L. dusaulti (Dufour 1821)], and Somalolydus (including species of the bifoveiceps group) are described. The first instar larva of L. dusaulti is described. Larval morphology confirms the inclusion of Lydomorphus in the tribe Lyttini. The characters of Lyttini larvae are briefly discussed.

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