Methamphetamine (METH) is a psychostimulant that induces neural damage in experimental animals and humans. A binge (usually in the 5-10 mg/kg dose range 4× at 2 h intervals) and the acute bolus drug administration (20-40 mg/kg) of METH have been employed frequently to study neurotoxicity in the brain. In this study we have compared these drug delivery schedules to determine their efficacy to induce striatal apoptosis. Exposure of male mice to a binge of METH at 10 mg/kg 4× at 2 h intervals (cumulative dose of 40 mg/kg) was approximately four times less effective in inducing apoptotic cell death (TUNEL staining) 24 h after METH treatment in the striatum than a single bolus administration of 30 mg/kg of METH. The residual TUNEL staining observed three days after METH treatment is proportionately equivalent between a binge and the acute bolus drug administration. Interestingly, a binge of METH induces a hyperthermic response of longer duration. This study demonstrates that an acute bolus drug administration of METH is more effective inducing striatal apoptosis in mice, and therefore, is more suitable for studies assessing the impact of METH on sites post-synaptic to the striatonigral dopamine terminals.
Methamphetamine (METH) is a highly addictive compound that induces toxicity of the dopamine (DA) terminals of the neostriatum. Exposure to METH induces long-term deficits in dopamine transporter (DAT) and tyrosine hydroxylase (TH) levels as well as induction of glial fibrillary acidic protein (GFAP) in the caudate putamen (CPu) and the nucleus accumbens (NAc). The primary effect of exposure to METH is elevation of the level of extracellular DA; therefore, we assessed the role of the DA D1 receptor (D1R) and neurokinin-1 receptor (NK-1R) on the expression of toxicity. METH was injected intraperitoneally (10 mg/kg) four times at 2-h intervals (an acute toxic dose), and the mice were sacrificed three days after the treatment. Exposure to METH resulted in marked reduction of DAT sites (reduced to 30 and 21% relative to control in medial and lateral aspects of the CPu) assessed by binding of [ 125 I]RTI-121 by autoradiography or Western blot analysis. Pretreatment with the nonpeptide NK-1R antagonist WIN-51,708 (10 mg/kg) 30 min prior to the first and fourth injections of METH prevented the loss of DAT sites of the CPu. Moreover, pretreatment with WIN-51,708 also prevented the reduction of TH levels induced by METH as well as the induction of GFAP in astrocytes. Pretreatment with the D1R antagonist SCH-23390 (0.25 mg/kg) 30 min before the first and fourth injections of METH conferred partial protection on DAT sites of the CPu. These results demonstrate that receptors postsynaptic to the DA terminals of the CPu are needed in order to express the neurotoxic effects of METH on integral components of the DA terminals of the nigrostriatal projection.
Eigenvalues and Eigenvectors are usually taught toward the middle of the semester and this modulo can be implemented right after the topics of diagonalization. Comparing to the other modulo, students will see applications of some advance topics. This also shows one quick application of eigenvalues and eigenvectors in environmental science. There are different types of modeling for the population growth but in this modulo we will introduce the Leslie type's matrix to model population. More appropriately, this modulo belongs to the realm of "population ecology".
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