Testosterone enhances dopamine depletion by methamphetamine in male, but not female, mice

Lewis, Chandani; Dluzen, Dean E.

doi:10.1016/j.neulet.2008.10.011

Cited by 30 publications

(23 citation statements)

References 37 publications

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“…Surprisingly, replacement of physiological levels of estradiol, but not nonaromatizable androgens, reversed the effect of castration in the rat PD model , suggesting that circulating testosterone promotes lesion size only after aromatization to estradiol. Although estradiol has been reported to have some protective capacity in male mice of the C57BL/6 strain, which are highly sensitive to MPTP (Ekue et al, 2002;Bourque et al, 2009), reports regarding other male mouse models (CD-1 strain) indicate that systemic estradiol is not neuroprotective Yu and Wagner, 1994;Gao and Dluzen, 2001;Lewis and Dluzen, 2008). On balance, the data suggest that both the response of the NSDA 174 system to injury and the protective effects of estrogen are sexually dimorphic.…”

Section: Gonadal Factors Are Protective In Female But Not In Male Ementioning

confidence: 89%

“…Moreover, very high doses of estradiol may fail to protect and may even worsen lesion size (Ramirez et al, 2003;Bourque et al, 2009). Fewer studies have been performed in male rodents, but in contrast to females, gonadal hormones exacerbate the extent of mild/moderate striatal lesions Murray et al, 2003;Lewis and Dluzen, 2008;Gillies and McArthur, 2010). Surprisingly, replacement of physiological levels of estradiol, but not nonaromatizable androgens, reversed the effect of castration in the rat PD model , suggesting that circulating testosterone promotes lesion size only after aromatization to estradiol.…”

Section: Gonadal Factors Are Protective In Female But Not In Male Ementioning

confidence: 98%

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Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines

2010

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Section: Gonadal Factors Are Protective In Female But Not In Male Ementioning

confidence: 89%

Section: Gonadal Factors Are Protective In Female But Not In Male Ementioning

confidence: 98%

Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines

2010

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“…In males, T also has a detrimental effect in experimental PD caused by methamphetamine treatment [125,126]. Interestingly, as recently reported in rat immortalized mesencephalic dopaminergic neuronal cell line, T or DHT treatment was protective when oxidative stress levels are minimal, but was detrimental when oxidative stress levels are elevated [127].…”

Section: May the Plasma Levels Of Neuroactive Steroids Be Considered mentioning

confidence: 59%

New steps forward in the neuroactive steroid field

Giatti

Garcia-Segura

Melcangi

2015

The Journal of Steroid Biochemistry and Molecular Biology

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“…For example, sex, hormonal factors and adrenergic blockers all affect the degree of MAinduced neurotoxicity [11][12][13][14][15][16]. A summary of the pair wise differences in MA-induced neurotoxicity (dorsal striatal dopamine depletion) for these three different factors, along with the corresponding changes in body weight to MA is illustrated in panels A-C of the figure 1.…”

mentioning

confidence: 99%

“…All data presented represent studies that had been approved by the IACUC at the Northeast Ohio Medical University (NEOMED). Data were compiled from the following sources: Panel A [14]; Panel B [13,15]; Panel C [16]; Panel D [21].…”

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confidence: 99%

Is Body Weight Loss a Harbinger of Methamphetamine-induced Neurotoxicity?

Dluzen¹

2013

J Addict Res Ther

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Methamphetamine (MA) is a drug of abuse of societal concern. Euphoria, increased energy/alertness and enhanced libido all contribute to the appeal, and therefore, abuse of this psychostimulant. Weight loss represents still another attribute of MA as indicated in both human [1][2][3][4] and animal [5,6] studies. In fact, weight loss has been reported as a reason for MA use [7][8][9] and MA under the trademark name Desoxyn, has been approved for use clinically in the treatment of exogenous obesity, as well as for ADHD and narcolepsy [10].In animal studies, MA has served as an agent to induce neurotoxicity within the Nigrostriatal Dopaminergic (NSDA) system, and thus a means to study conditions that modulate this neurotoxicity. For example, sex, hormonal factors and adrenergic blockers all affect the degree of MAinduced neurotoxicity [11][12][13][14][15][16]. A summary of the pair wise differences in MA-induced neurotoxicity (dorsal striatal dopamine depletion) for these three different factors, along with the corresponding changes in body weight to MA is illustrated in panels A-C of the figure 1. In all three situations, conditions showing greater amounts of dopamine depletion (A-males versus females, B-testosterone (TP) versus sesame oil vehicle treated controls, C-Propranolol (PROP) versus Prazosin (PRAZ)) are associated with the greater amounts of body weight reductions.A cursory and seemingly obvious conclusion would be that the greater extent of neurotoxicity produces a corresponding greater degree of generalized malaise, as indicated by body weights. The data presented in panel D of the figure 1 suggest that this may not necessarily be the case. Here are presented results obtained using a similar sex-differences protocol as that presented in panel A, however, with NSDA neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). While nearly identical dorsal striatal dopamine reductions are obtained with MA and MPTP (A versus D), the corresponding sex differences in body weight present to MA, are completely absent with MPTP (A versus D). Such results suggest that sex differences in response to neurotoxins targeting the NSDA system do not inescapably generate identical changes in body weights. Rather, body weight reductions following MA treatment appear to be closely associated with the degree of NSDA loss and are specific for MA-induced NSDA neurotoxicity.Confirmation or refutation of this intriguing relationship awaits further investigation involving formal experiments on dose-response, time-course, cross-species analyses and food restriction/palatability. Moreover, differences in MA regimes between the mouse models as described above and the clinical/street use of this drug also warrant consideration in evaluating this relationship. While remaining cognizant of these limitations, data derived from these animal experiments have served as relatively valid and reliable models for indices of effects in humans. Women show less toxicity [17] and diminished dopamine responses [18] to MA/amphetami...

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Testosterone enhances dopamine depletion by methamphetamine in male, but not female, mice

Cited by 30 publications

References 37 publications

Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines

Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines

New steps forward in the neuroactive steroid field

Is Body Weight Loss a Harbinger of Methamphetamine-induced Neurotoxicity?

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