Lobeline attenuates methamphetamine-induced changes in vesicular monoamine transporter 2 immunoreactivity and monoamine depletions in the striatum.
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.
Laboratory of Neurochemistry, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA 02118, USA.
David J
DJ
Eyerman
Bryan K
BK
Yamamoto
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D008120:Lobeline / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008694:Methamphetamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D018663:Adrenergic Agents; D015306:Biogenic Monoamines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D008694:Methamphetamine; D008120:Lobeline