Effects of high‐dose methamphetamine on monoamine uptake sites in rat brain measured by quantitative autoradiography

Abstract

The neurotoxicity of methamphetamine to monoaminergic neurons was examined. Neurotoxicity was assessed by quantitative autoradiography using radioligands specific for binding to norepinephrine, dopamine, and serotonin uptake sites. High-dose administration of methamphetamine led to decreases in binding to uptake sites for the three monoamines. Norepinephrine binding sites were decreased in certain amygdaloid nuclei and in the dorsomedial hypothalamic nucleus. Serotonin binding sites were reduced in widespread brain areas, while dopamine binding sites were reduced in the caudate putamen, olfactory tubercle, and nucleus accumbens. The decreases in binding site density for the three monoamines are limited to terminal field areas; cell body areas are not affected. Our results indicate that methamphetamine is neurotoxic to serotonin, dopamine, and norepinephrine neurons. The neurotoxicity to norepinephrine neurons is in selected brain areas.

Effect of single and repeated methamphetamine treatment on neurotransmitter release in substantia nigra and neostriatum of the rat

“…As shown in Tables 3 and 4, K + -depolarization in neostriatum produced a significant increase of striatal, but also of nigral Dyn B levels, indicating a monosynaptic interaction. While the effect of high doses of Meth on DA release has been extensively demonstrated (O'Dell et al 1991;Kuczenski and Segal 1992;Nash and Yamamoto 1992;Abekawa et al 1994), this is the first time that the effect of Meth on monoamines, amino acids and neuropeptides is simultaneously analysed in substantia nigra and neostriatum, which is relevant, as the neurotoxic effect of Meth has been observed in terminals, but not in cell body regions (Brunswick et al 1992).…”

“…The long-term effects of Meth are largely restricted to the nigrostriatal DA system (Ricaurte et al 1980;Marshall and Navarrete 1990;Marshall et al 1993;Burrows and Meshul 1997). Short-and long-term effects have also been described in limbic and cortical systems, but these systems are less and differently affected than the neostriatum (Axt and Molliver 1991;Brunswick et al 1992;Eisch et al 1996). Furthermore, while, as measured by quantitative autoradiography, the neurotoxic effect of Meth is seen in widespread brain regions receiving monoamine terminals, the cell body regions are largely unaffected (Brunswick et al 1992).…”

“…Short-and long-term effects have also been described in limbic and cortical systems, but these systems are less and differently affected than the neostriatum (Axt and Molliver 1991;Brunswick et al 1992;Eisch et al 1996). Furthermore, while, as measured by quantitative autoradiography, the neurotoxic effect of Meth is seen in widespread brain regions receiving monoamine terminals, the cell body regions are largely unaffected (Brunswick et al 1992). It has been proposed that the long-term effects of Meth depend on the amount of overflow of DA induced by the drug (O'Dell et al 1991), and, in agreement, it has been shown that Meth-induced damage is prevented by inhibition of DA synthesis (Gibb and Kogan 1979;Hotchkiss and Gibb 1980;, DA transport Marek et al 1990), or even by DA receptor antagonism (Sonsalla et al 1986;O'Dell et al 1993).…”

Effects of Repeated High-Dose Methamphetamine on Local Cerebral Glucose Utilization in Rats

“…However, the hippocampus also is innervated by the dorsal raphe efferents. Brunswick et al (1992) had demonstrated that high-dose MAP can decrease serotonin uptake site in this region. Sharkey et al (1991) examined the effects of repeated methylenedioxymethamphetamine (MDMA 20 mg/kg, s.c., twice daily for 4 days, 14 days later) upon hippocampal function by using the [14C]-2DG and [3H] paroxetine 5-HT binding site autoradiographic methods and found that profound losses of [3H] paroxetine labelled uptake sites accompanied by significant increases in LCGU in the hippocampal fields CA2, CA3 and dentate gyrus.…”

“…It is of interest that serotonergic raphe bodies appear to be resistant to the neurotoxic effects of a number of neurotoxic amphetamine-like compounds (Brunswick et al 1992) The discrepancy may be due to the study method because the 2DG method detects the change in the synaptic activity rather than the neuron body.…”