Tamoxifen increases methamphetamine-evoked dopamine output from superfused striatal tissue fragments of male mice.
The antiestrogen, tamoxifen (TMX), has been shown to function as a neuroprotectant against the nigrostriatal dopaminergic (NSDA) neurotoxin, methamphetamine (MA), within male mice. In the present report, we examined the effects of a combined infusion of TMX and MA within superfused striatal tissue fragments of male mice as an approach to understand some of the bases for TMX to function as a NSDA neuroprotectant within male mice. In Experiment 1, a coinfusion of TMX at 1, 10, or 100 pg/ml were all equally effective in increasing MA-evoked dopamine (DA) output as compared with a 0 pg/ml (control) dose. In Experiment 2, we tested whether this effect of TMX was specific for MA-evoked DA output by coinfusing TMX with a depolarizing concentration of potassium chloride (K+ -30 mM). No statistically significant differences were obtained between superfusions of striatal tissue fragments stimulated with K+ in the presence or absence of TMX (100 pg/ml). In Experiment 3, we assessed whether these effects of TMX may be exerted upon the dopamine transporter (DAT) by coinfusing DA (1 microM) in the presence or absence of TMX (100 pg/ml). No differences in DA recovery rates were obtained between superfusions performed in the presence or absence of TMX. Taken together, these results show that the striatum of male mice is very sensitive to the modulatory effects of TMX upon MA-evoked DA output. These effects of TMX appear to be relatively specific for MA-evoked DA output, as K+ -stimulated DA was not altered by TMX, and do not appear to exert these effects by altering dopamine transporter function.
Willett
Matthew C
MC
Department of Anatomy, Northeastern Ohio Universities College of Medicine (NEOUCOM), 4209 State Route 44, PO Box 95, Rootstown, OH 44272-0095, USA.
Dluzen
Dean E
DE
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins; D004357:Drug Synergism; D004965:Estrogen Antagonists / Q000494:pharmacology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*
D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D004965:Estrogen Antagonists; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493215:Slc6a3 protein, mouse; D013629:Tamoxifen; D008694:Methamphetamine; D004298:Dopamine