The effects of amfonelic acid, a dopamine uptake inhibitor, on methamphetamine-induced dopaminergic terminal degeneration and astrocytic response in rat striatum

Disparity in the temporal appearance of methamphetamine-induced apoptosis and depletion of dopamine terminal markers in the striatum of mice

“…Both dose schedules of METH induce GFAP in striatal astrocytes [12]. However, a study suggests that this astrocytic response may be due to degenerating corticostriatal fibers since GFAP induction was observed in the absence of depletion of striatal TH [24]. Our results suggest that degenerating striatal neurons may also contribute to the induction of the astrocytic response since TUNEL staining precedes the peak of GFAP induction in striatal astrocytes.…”

“…In recent years, it was discovered that METH induces apoptotic cell death in the striatal neurons that are post-synaptic to the DA terminals [7,8,24,42,45]. Thus, in the light that METH induces both pre-and post-synaptic neural damage, a question that arises is whether METH-induced apoptotic cell death and DA terminal toxicity appear simultaneously or whether these events peak at different times after METH.…”

Changes in Gene Expression Linked to Methamphetamine-Induced Dopaminergic Neurotoxicity

“…To identif y relevant gene expression patterns, microarray studies were performed in combination with a targeted pharmacological strategy designed to facilitate recognition of changes in gene expression patterns that were directly linked to the neurotoxic process. In particular, because early critical stages of M ETH-induced DA neurotoxicity take place within a well defined time frame (Ͻ24 hr after M ETH administration) (Ricaurte et al, 1982;Marek et al, 1990a), and because the toxic effects of M ETH on DA neurons can be completely blocked with DAT inhibitors (Ricaurte et al, 1984;Marek et al, 1990a,b;Pu et al, 1994Pu et al, , C allahan et al, 2001, we reasoned that by comparing mRNA expression patterns in the presence and absence of a DAT inhibitor (W I N35,428) within 24 hr after M ETH administration, we might be able to identif y a gene expression pattern ("signature") associated with early stages of M ETH-induced neurotoxicity (see below). Choice of the DAT inhibitor W I N35,428 was on the basis of findings from previous studies indicating that its DA neuroprotective effect is independent of effects on temperature (C allahan et al, 2001).…”

“…However, a considerable body of data attests to the importance of DA transporter (DAT) function and temperature. The essential role of the DAT in METH-induced DA neurotoxicity has been demonstrated by the observation that DAT inhibitors afford complete neuroprotection (Ricaurte et al, 1984; Marek et al, 1990a,b;Pu et al, 1994) and the finding that DAT knock-out mice are insensitive to METH neurotoxicity (Fumagalli et al, 1998). The importance of temperature has been documented by studies demonstrating that decreases in core temperature protect against METH neurotoxicity, whereas increases in core temperature exacerbate the toxicity (Bowyer et al, 1994;Miller and O'Callaghan, 1994;Albers and Sonsalla, 1995;Ali et al, 1996).…”

Causes and consequences of methamphetamine and MDMA toxicity

“…For instance, in rats, METH has been shown to increase silver-and fl uoro-Jadestaining. [29][30][31] Similarly, glial fi brillary fl uorescent protein (GFAP), a marker for central nervous system (CNS) trauma or injury 32 has been reliably induced by METH treatment in rats 33 and mice. 34 Unlike the multiple histochemical studies supporting that METH could produce axonal degeneration, little evidence for degenerating neurons has been shown after MDMA administration.…”