Summary
The administration of high doses of methamphetamine to mice causes long-lasting depletions of striatal dopamine to a greater extent in males than in females. Likewise, the incidence of Parkinson's disease is higher in males than in females. The present study investigated the roles of estrogen and testosterone in mediating the dopamine depletion induced by methamphetamine. Male and female mice received four cumulative SC doses of methamphetamine (10 mg/kg) at two hour intervals and were sacrificed two weeks later for HPLC analysis of striatal monoamines. Intact male mice were found to have a 76% dopamine depletion, which was significantly greater than the 37% depletion exhibited by the intact female mice. Neither removal of the ovaries nor removal of the testes one month prior to the methamphetamine treatment significantly changed the magnitude of the methamphetamine-induced dopamine depletion. Thus, the reduced sensitivity of female mice to methamphetamine may be independent of physiological gonadal hormones.
Similar content being viewed by others
References
Ayd FJ Jr (1961) Neuroleptic and extrapyramidal reactions in psychiatric patients. In: Bordeleau JM (ed) Extrapyramidal system and neuroleptics. Editions Psychiatric, Montreal, pp 355–363
Becker JB (1990) Direct effect of 17B-estradiol on striatum: sex differences in dopamine release. Synapse 5: 157–164
Bitar MS, Ota M, Linnoila M, Shapiro BH (1991) Modification of gonadectomy-induced increases in brain monoamine metabolism by steroid hormones in male and female rats. Psychoneuroendocrinology 16: 547–557
Brooks WJ, Jarvis MF, Wagner GC (1989) Influence of sex, age, and strain of MPTP-induced neurotoxicity. Res Comm Subst Abuse 10: 181–184
Davis GC, Williams AC, Markey SP, Ebert MH, Caine E, Reichert CM, Kopin I (1979) Chronic parkinsonism secondary to intravenous injection of meperidine analogues. Psychiat Res 1: 249–254
De Vito MJ, Wagner GC (1989) Functional consequences following methamphetamine-induced neuronal damage. Psychopharmacology 97: 432–435
Diamond SG, Markham CH, Hoehn MM, McDowell FH, Muenter M (1990) An examination of male-female differences in progression and mortality of Parkinson's disease. Neurology 40: 763–766
Dluzen DE, Ramirez VD (1989) Effects of orchidectomy on nigrostriatal dopaminergic function: behavioral and physiological evidence. J Neuroendocrinol 1: 285–290
Dluzen DE, Jain R, Liu B (1994) Modulatory effects of testosterone on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity. J. Neurochem 62 (1): 94–101
Hartesveldt CV, Joyce JN (1986) Effects of estrogen on the basal ganglia. Neurosci Biobehav Rev 10: 1–14
Jenner P, Marsden CD (1986) The actions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in animals as a model of Parkinson's disease. J Neural Transm [Suppl 20]: 11–39
Johnson WG (1991) Genetic susceptibility to Parkinson's disease. Neurology 41 [Suppl 2]: 82–87
Johnson WG, Hodge SE, Duvoisin R (1990) Twin studies and the genetics of Parkinson's disease—a reappraisal. Mov Disord 5: 187–194
Johnson SK, Medina D, Wagner GC (1992) The effects of deprenyl on methamphetamine-induced dopamine depletions. J Neural Transm 89: 123–127
Langston JW, Ballard PA, Tetrud, JW, Irwin I (1983) Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219: 979–980
Lillienfeld D (1990) Two decades of increasing motality from Parkinson's disease among the US elderly. Arch Neurol 47: 731–734
Roof RL, Duvdevani R, Stein DG (1993) Gender influences outcome of brain injury: progresterone plays a protective role. Brain Res 607: 333–336
Seiden LS, Vosmer G (1984) Formation of 6-hydroxydopamine in caudate nucleus of the rat brain after a single dose of methamphetamine. Pharmacol Biochem Behav 21: 29–31
Seiden LS, Fischman MW, Schuster CR (1975/76) Long-term methamphetamine induced changes in brain catecholamines in tolerant rhesus monkeys. Drug Alcohol Depend 1: 215–221
Semchuk KM, Love EJ, Lee RG (1993) Parkinson's disease: a test of the multifactorial etiologic hypothesis. Neurology 43: 1173–1180
Tepper SJ, Haas JF (1979) Prevalence of tardive, dyskinesia. J Clin Psychiatry 40: 508–516
Wagner GC, Ricaurte GA, Seiden LS, Schuster CR, Miller JM, Westly J (1980) Longlasting depletion of striatal dopamine and loss of dopamine uptake sites following the repeated administration of methamphetamine. Brain Res 181: 151–160
Wagner GC, Seiden LS, Schuster CR (1979) Methamphetamine-induced changes in brain catecholamines in rats and guinea pigs. Drug Alcohol Depend 4: 435–438
Wagner GC, Tekirian TL, Cheo CT (1993) Sexual differences in sensitivity to methamphetamine toxicity. J Neural Transm 93: 67–70
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yu, Y.L., Wagner, G.C. Influence of gonadal hormones on sexual differences in sensitivity to methamphetamine-induced neurotoxicity. J Neural Transm Gen Sect 8, 215–221 (1994). https://doi.org/10.1007/BF02260942
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02260942