title: Methamphetamine exacerbates the toxic effect of kainic acid in the adult rat retina.
abstract: The recreational use of the psychoactive drug, methamphetamine has increased markedly over the last three decades. It has long been known that this drug has detrimental effects upon the mammalian brain monoaminergic system, but the long- or short-term effects on the retina, a neurological extension of the central nervous system, have received little attention. The aim of this study was, therefore, to determine whether intraocular injection of methamphetamine (MA) is toxic to the healthy adult rat retina and to analyse its effects on the compromised retina after an injection of the ionotropic glutamate receptor agonist, kainate, which is known to cause retinal neuropathology. The equivalent of 1 mM (in the vitreous humour) MA and/or kainate (40 microM) were injected intravitreally. Flash electroretinograms (ERGs) were recorded before and 2 and 4 days after treatment. Five days after treatment, animals were killed and the retinas analysed either for the immunohistochemical localisation of various antigens or for electrophoresis/Western blotting. Some animals were kept for 19 days after treatment and the retinas analysed for tyrosine hydroxylase immunoreactivity. No differences could be found between vehicle- and MA-treated retinas with respect to the nature or localisation of either tyrosine hydroxylase immunoreactivity after 5 or 19 days or other antigens after 5 days. Moreover, the normal ERG and GFAP and calretinin protein antigens were unaffected by MA. Kainate treatment, however, caused a change in the ERGs after 2 and 4 days, an alteration in every antigen localised by immunohistochemistry and an increase in the retinal levels of calretinin and GFAP proteins. Significantly, the changes seen in the b-wave amplitude and implicit time of the ERG after 4 days and the increased level of GFAP protein after 5 days following kainate treatment were enhanced when MA was co-injected. Intravitreal injection of methamphetamine had no detectable detrimental effect on the normal adult rat retina but exacerbated the damaging effects of kainic acid. Such data suggest that a neurotoxic effect of MA may be more obviously illustrated when the tissue is already compromised as occurs in, for example, ischemia.
authors.affiliation: Nuffield Laboratory of Ophthalmology, Oxford University, Walton Street, Oxford OX2 6AW, UK. lorena@ibmc.up.pt
authors.forename: L G
authors.initials: LG
authors.lastname: Rodrigues
authors.forename: M A
authors.initials: MA
authors.lastname: Tavares
authors.forename: J P M
authors.initials: JP
authors.lastname: Wood
authors.forename: K-G
authors.initials: KG
authors.lastname: Schmidt
authors.forename: N N
authors.initials: NN
authors.lastname: Osborne
mesh_terms: D000818:Animals; D015153:Blotting, Western; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000633:toxicity*; D003623:Dark Adaptation / Q000502:physiology; D004357:Drug Synergism; D004596:Electroretinography; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005123:Eye; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007267:Injections; D007608:Kainic Acid / Q000633:toxicity*; D008694:Methamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D010775:Photic Stimulation; D051381:Rats; D012160:Retina / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D008694:Methamphetamine; D014446:Tyrosine 3-Monooxygenase; D007608:Kainic Acid