Ontogeny of methamphetamine-induced neurotoxicity and associated hyperthermic response

Brain Research. Developmental Brain Research
G D CapponC V Vorhees

Abstract

Methamphetamine (MA) administration to adult rats results in neurotoxicity characterized by depletion of caudate-putamen (CP) dopamine (DA) and serotonin (5-HT) and an accompanying increase in glial fibrillary acidic protein (GFAP) content. The severity of MA-induced neurotoxicity correlates with the accompanying thermoregulatory response, i.e., a hyperthermic response facilitates neurotoxicity while a hypothermic response is neuroprotective. In the following study, the thermoregulatory and neurotoxic effects of MA administration (4 x 10 mg/kg) were investigated in developing rats at postnatal days (PND) 20, 40 and 60. Rats at PND 20 and PND 40 were administered MA at ambient temperatures of 22 degrees C and 30 degrees C; and PND 60 rats were administered MA at 22 degrees C only. Temperatures were measured and thermal responses were compared by calculating the total thermal response (TTR) induced by MA treatment. MA administration to PND 60 rats at 22 degrees C induced a hyperthermic response, resulted in a 47% reduction of neostriatal DA and a 49% increase of GFAP content. Administration of MA to PND 40 rats at 22 degrees C failed to induce a hyperthermic response and did not result in reduced DA or increased GFAP. However, ad...Continue Reading

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