TY - JOUR T1 - Lobeline Attenuates Methamphetamine-Induced Changes in Vesicular Monoamine Transporter 2 Immunoreactivity and Monoamine Depletions in the Striatum JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 160 LP - 169 DO - 10.1124/jpet.104.072264 VL - 312 IS - 1 AU - David J. Eyerman AU - Bryan K. Yamamoto Y1 - 2005/01/01 UR - http://jpet.aspetjournals.org/content/312/1/160.abstract N2 - l-Lobeline is an alkaloid that inhibits the behavioral effects of methamphetamine (METH) in rats. No studies have examined the effects of lobeline on the acute and long-term neurochemical changes produced by neurotoxic doses of METH. The effects of lobeline on METH-induced dopamine release, alterations in vesicular monoamine transporter 2 (VMAT-2) distribution, and long-term depletions of dopamine and serotonin (5-HT) content in the rat striatum were examined. METH increased body temperature and dopamine release, decreased VMAT-2 immunoreactivity at 1 and 24 h after METH, and decreased dopamine and 5-hydroxytryptamine (5-HT) content in striatum when examined 7 days later. Prevention of METH-induced hyperthermia attenuated the decrease in VMAT-2 as well as dopamine and 5-HT content. Lobeline pretreatment did not affect METH-induced dopamine release but attenuated the decreases in VMAT-2 after METH and the long-term decreases in striatal dopamine and 5-HT content. These effects of lobeline were due partly to the attenuation of METH-induced hyperthermia. The maintenance of hyperthermia during lobeline + METH exposure restored the effects of METH on decreases in VMAT-2 as well as dopamine and 5-HT content. To examine the effects of lobeline independent of its effects on METH-induced hyperthermia, lobeline was administered after METH when body temperature returned to normal. Lobeline treatment at 5 and 7 h after METH attenuated the METH-induced decreases in synaptosomal, membrane-associated, and vesicular VMAT-2 24 h after METH, as well as the METH-induced decreases in dopamine and 5-HT content 7 days later. Therefore, lobeline has both temperature-dependent and -independent neuroprotective effects against METH toxicity. The American Society for Pharmacology and Experimental Therapeutics ER -