Histological and ultrastructural evidence thatd-amphetamine causes degeneration in neostriatum and frontal cortex of rats

Ryan, Lawrence J.; Linder, Jean C.; Martone, Maryann E.; Groves, Philip M.

doi:10.1016/0006-8993(90)90955-b

Cited by 119 publications

(76 citation statements)

References 30 publications

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“…FJB is a fluorescent dye that has high affinity for degenerating neurons, regardless of specific insult or mechanism of cell death (Schmued and Hopkins, 2000). Consistent with previous reports (Ryan et al, 1990;Schmued and Bowyer, 1997;Deng et al, 2001), neurodegeneration occurred in the frontoparietal and piriform cortices and in the striatum (Figure 1a), in METH-treated both FosB( + / + ) and (À/À) mice. We found some FJB-positive neurons in the hippocampal complex as well, but to a much lesser extent (data not shown).…”

Section: Enhanced Meth Neurotoxicity In Fosb(à/à) Micesupporting

confidence: 89%

FosB Null Mutant Mice Show Enhanced Methamphetamine Neurotoxicity: Potential Involvement of FosB in Intracellular Feedback Signaling and Astroglial Function

Kuroda

Ornthanalai

Kato

et al. 2009

Neuropsychopharmacol

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Previous studies show that (1) two members of fos family transcription factors, c-Fos and FosB, are induced in frontal brain regions by methamphetamine; (2) null mutation of c-Fos exacerbates methamphetamine-induced neurotoxicity; and (3) null mutation of FosB enhances behavioral responses to cocaine. Here we sought a role of FosB in responses to methamphetamine by studying FosB null mutant (À/À) mice. After a 10 mg/kg methamphetamine injection, FosB(À/À) mice were more prone to self-injury. Concomitantly, the intracellular feedback regulators of Sprouty and Rad-Gem-Kir (RGK) family transcripts had lower expression profiles in the frontoparietal cortex and striatum of the FosB(À/À) mice. Three days after administration of four 10 mg/kg methamphetamine injections, the frontoparietal cortex and striatum of FosB(À/À) mice contained more degenerated neurons as determined by Fluoro-Jade B staining. The abundance of the small neutral amino acids, serine, alanine, and glycine, was lower and/or was poorly induced after methamphetamine administration in the frontoparietal cortex and striatum of FosB(À/À) mice. In addition, methamphetamine-treated FosB(À/À) frontoparietal and piriform cortices showed more extravasation of immunoglobulin, which is indicative of blood-brain barrier dysfunction. Methamphetamine-induced hyperthermia, brain dopamine content, and loss of tyrosine hydroxylase immunoreactivity in the striatum, however, were not different between genotypes. These data indicate that FosB is involved in thermoregulation-independent protective functions against methamphetamine neurotoxicity in postsynaptic neurons. Our findings suggest two possible mechanisms of FosB-mediated neuroprotection: one is induction of negative feedback regulation within postsynaptic neurons through Sprouty and RGK. Another is supporting astroglial function such as maintenance of the blood-brain barrier, and metabolism of serine and glycine, which are important glial modulators of nerve cells.

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Section: Enhanced Meth Neurotoxicity In Fosb(à/à) Micesupporting

confidence: 89%

FosB Null Mutant Mice Show Enhanced Methamphetamine Neurotoxicity: Potential Involvement of FosB in Intracellular Feedback Signaling and Astroglial Function

Kuroda

Ornthanalai

Kato

et al. 2009

Neuropsychopharmacol

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“…It is also important to note that it is not neurotoxic to dopamine neurons, as is the case with continuous amphetamine administration or with much higher dose regimens. As might be expected, amphetamine neurotoxicity is associated with signs of cellular degeneration (Ricaurte et al, 1982;Ryan et al, 1990).…”

Section: Methodsmentioning

confidence: 58%

Persistent Structural Modifications in Nucleus Accumbens and Prefrontal Cortex Neurons Produced by Previous Experience with Amphetamine

1997

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Experience-dependent changes in behavior are thought to involve structural modifications in the nervous system, especially alterations in patterns of synaptic connectivity. Repeated experience with drugs of abuse can result in very long-lasting changes in behavior, including a persistent hypersensitivity (sensitization) to their psychomotor activating and rewarding effects. It was hypothesized, therefore, that repeated treatment with the psychomotor stimulant drug amphetamine, which produces robust sensitization, would produce structural adaptations in brain regions that mediate its psychomotor activating and rewarding effects. Consistent with this hypothesis, it was found that amphetamine treatment altered the morphology of neurons in the nucleus accumbens and prefrontal cortex. Exposure to amphetamine produced a long-lasting (Ͼ1 month) increase in the length of dendrites, in the density of dendritic spines, and in the number of branched spines on the major output cells of the nucleus accumbens, the medium spiny neurons, as indicated by analysis of Golgi-stained material. Amphetamine treatment produced similar effects on the apical (but not basilar) dendrites of layer III pyramidal neurons in the prefrontal cortex. The ability of amphetamine to alter patterns of synaptic connectivity in these structures may contribute to some of the long-term behavioral consequences of repeated amphetamine use, including amphetamine psychosis and addiction.

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“…Thus, where there is evidence of specific cognitive impairments in shifting behavior or in decision-making (Rogers et al 1999b) such deficits may exacerbate those patterns of behavior leading to further drug abuse, perhaps as ancillary neurotoxic consequences of drug abuse. There is an extensive literature on neurotoxic effects of amphetamine and related drugs in experimental animals, although it can be questioned to what extent such toxicity might be expressed in human drug abusers (Ricaurte et al 1984;Ryan et al 1990;Melega et al 1996). Nevertheless, recent studies (e.g., Kolb 1997, 1999) are now demonstrating apparently long-lasting changes in dendritic branching in brain regions such as the nucleus accumbens and parietal and prefrontal cortex, of repeated injections of single doses of morphine or amphetamine in ranges relevant to reinforcing effects.…”

Section: Discussionmentioning

confidence: 99%

Profiles of Cognitive Dysfunction in Chronic Amphetamine and Heroin Abusers

Ornstein

Iddon

Baldacchino

et al. 2000

Neuropsychopharmacology

389

291

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Histological and ultrastructural evidence thatd-amphetamine causes degeneration in neostriatum and frontal cortex of rats

Cited by 119 publications

References 30 publications

FosB Null Mutant Mice Show Enhanced Methamphetamine Neurotoxicity: Potential Involvement of FosB in Intracellular Feedback Signaling and Astroglial Function

FosB Null Mutant Mice Show Enhanced Methamphetamine Neurotoxicity: Potential Involvement of FosB in Intracellular Feedback Signaling and Astroglial Function

Persistent Structural Modifications in Nucleus Accumbens and Prefrontal Cortex Neurons Produced by Previous Experience with Amphetamine

Profiles of Cognitive Dysfunction in Chronic Amphetamine and Heroin Abusers

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