Cocaine neurotoxicity and altered neuropeptide Y immunoreactivity in the rat hippocampus; a silver degeneration and immunocytochemical study.
- Authors
- Goodman, J H; Sloviter, R S
- Year
- 1993
- Journal
- Brain research
- PMID
- 8358618
- DOI
- 10.1016/0006-8993(93)90217-b
Neuroanatomical methods were used to determine if cocaine irreversibly injures neurons. Despite acute and chronic high-dose treatments for months that produced stereotyped behavior and seizures, and the use of a sensitive silver impregnation method, we were unable to find any evidence of neuronal damage anywhere in the brain. Since expression of the inducible 72 kDa heat shock protein (HSP72) is a sensitive indicator of potentially toxic neuronal stress, we next determined if cocaine evoked HSP72 expression. Even high doses of cocaine that evoked seizures did not induce HSP72 immunoreactivity anywhere within the brain, whereas kainic acid produced widespread HSP72 immunoreactivity and irreversible injury. Having failed to find indications of frank neurotoxicity, we examined peptide and protein cell marker immunoreactivities in search of cocaine-induced changes. Although cocaine treatment had no obvious effects on the patterns of hippocampal calbindin-D28K, somatostatin-, tyrosine hydroxylase- and parvalbumin immunoreactivities, cocaine reliably altered neuropeptide Y-like immunoreactivity (NPY-LI). Most notably, NPY-LI was expressed in hippocampal dentate granule cells and pyriform cortical neurons, which do not normally express it. Conversely, we noted decreased NPY-LI in dentate hilar neurons that normally do express it. Since both changes in NPY-LI were seen only in cocaine-treated rats that exhibited seizures, the role of seizure activity per se in producing the NPY changes was addressed in normal rats by electrical stimulation of the perforant path. Like cocaine, perforant path stimulation for as little as 15min evoked NPY-LI in granule cells but did not replicate the cocaine-induced decrease in hilar cell NPY-LI. These results suggest that cocaine does not irreversibly injure neurons in the rat, even at doses that induce seizures. However, cocaine produces long-lasting changes in NPY expression that are of unknown functional significance. Our inability to demonstrate cocaine-induced neuronal damage in rats should in no way be taken as evidence of its safety in humans.
No figures extracted from this document.
No chunks — full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
No citations found.
In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Neuropeptide Y receptor genes are associated with alcohol dependence, alcohol withdrawal phenotypes, and cocaine dependence. | 2008 | 18828811 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Cross talk about the role of Neuropeptide Y in CNS disorders and diseases. | Bale R et al. | — | 2023 | → |
| Cyclohexane Inhalation Produces Long-Lasting Alterations in the Hippocampal Integrity and Reward-Seeking Behavior in the Adult Mouse. | Campos-Ordonez T et al. | — | 2019 | → |
| The long-term effects of cocaine use on cognitive functioning: A systematic critical review. | Frazer KM et al. | — | 2018 | → |
| Long-lasting memory deficits in mice withdrawn from cocaine are concomitant with neuroadaptations in hippocampal basal activity, GABAergic interneurons and adult neurogenesis. | Ladrón de Guevara-Miranda D et al. | — | 2017 | → |
| The impact of cocaine on adult hippocampal neurogenesis: Potential neurobiological mechanisms and contributions to maladaptive cognition in cocaine addiction disorder. | Castilla-Ortega E et al. | — | 2017 | → |
| The Role of Neuropeptide Y (NPY) in Alcohol and Drug Abuse Disorders. | Robinson SL et al. | — | 2017 | → |
| Effects of drugs of abuse on the central neuropeptide Y system. | Gonçalves J et al. | — | 2016 | → |
| Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse. | Korpi ER et al. | — | 2015 | → |
| Methamphetamine-induced changes in the mice hippocampal neuropeptide Y system: implications for memory impairment. | Gonçalves J et al. | — | 2012 | → |
| Neurotoxicity of anhydroecgonine methyl ester, a crack cocaine pyrolysis product. | Garcia RC et al. | — | 2012 | → |
| Protective role of neuropeptide Y Y₂ receptors in cell death and microglial response following methamphetamine injury. | Gonçalves J et al. | — | 2012 | → |
| Aging-induced Seizure-related Changes to the Hippocampal Mossy Fiber Pathway in Forebrain Specific BDNF Overexpressing Mice. | Weidner KL et al. | — | 2011 | → |
| Dopamine transporter down-regulation following repeated cocaine: implications for 3,4-methylenedioxymethamphetamine-induced acute effects and long-term neurotoxicity in mice. | Peraile I et al. | — | 2010 | → |
| Neuropeptide Y receptor genes are associated with alcohol dependence, alcohol withdrawal phenotypes, and cocaine dependence. | Wetherill L et al. | — | 2008 | → |
| Neurotoxic profiles of HIV, psychostimulant drugs of abuse, and their concerted effect on the brain: current status of dopamine system vulnerability in NeuroAIDS. | Ferris MJ et al. | — | 2008 | → |
| Modest thyroid hormone insufficiency during development induces a cellular malformation in the corpus callosum: a model of cortical dysplasia. | Goodman JH et al. | — | 2007 | → |
| Neuropeptide Y in the dentate gyrus. | Sperk G et al. | — | 2007 | → |
| Thyroid hormone insufficiency during brain development reduces parvalbumin immunoreactivity and inhibitory function in the hippocampus. | Gilbert ME et al. | — | 2007 | → |
| Cocaine-mediated enhancement of Tat toxicity in rat hippocampal cell cultures: the role of oxidative stress and D1 dopamine receptor. | Aksenov MY et al. | — | 2006 | → |
| Chronic developmental lead exposure reduces neurogenesis in adult rat hippocampus but does not impair spatial learning. | Gilbert ME et al. | — | 2005 | → |
| Cat exposure induces both intra- and extracellular Hsp72: the role of adrenal hormones. | Fleshner M et al. | — | 2004 | → |
| Neuropeptide Y and Epilepsy. | Colmers WF et al. | — | 2003 | → |
| Up-regulation of GABA(B) receptor mRNA and protein in the hippocampus of cocaine- and lidocaine-kindled rats. | Li J et al. | — | 2003 | → |
| Plasticity of Y1 and Y2 receptors and neuropeptide Y fibers in patients with temporal lobe epilepsy. | Furtinger S et al. | — | 2001 | → |
| Acute stress increases neuropeptide Y mRNA within the arcuate nucleus and hilus of the dentate gyrus. | Conrad CD et al. | — | 2000 | → |
| Neuropeptide Y-Y1 receptor antisense oligodeoxynucleotide increases the infarct volume after middle cerebral artery occlusion in rats. | Cheung RT et al. | — | 2000 | → |
| Choreoathetoid movements in cocaine dependence. | Bartzokis G et al. | — | 1999 | → |
| Differential potencies of cocaine and its metabolites, cocaethylene and benzoylecgonine, in suppressing the functional expression of somatostatin and neuropeptide Y producing neurons in cultures of fetal cortical cells. | Aguila-Mansilla N et al. | — | 1997 | → |
| Knock-out mice reveal a critical antiepileptic role for neuropeptide Y. | Baraban SC et al. | — | 1997 | → |
| Marked decrease of neuropeptide Y Y2 receptor binding sites in the hippocampus in murine prion disease. | Diez M et al. | — | 1997 | → |
| Neurochemical alterations in asymptomatic abstinent cocaine users: a proton magnetic resonance spectroscopy study. | Chang L et al. | — | 1997 | → |
| Induction of hsp 70 in HepG2 cells in response to hepatotoxicants. | Salminen WF et al. | — | 1996 | → |
| Selective upregulation of T alpha 1 alpha-tubulin and neuropeptide Y mRNAs after intermittent excitatory stimulation in adult rat hippocampus in vivo. | Causing CG et al. | — | 1996 | → |
| Adrenal steroid regulation of neuropeptide Y (NPY) mRNA: differences between dentate hilus and locus coeruleus and arcuate nucleus. | Watanabe Y et al. | — | 1995 | → |
| Cytotoxicity of the cocaine metabolite benzoylecgonine. | Lin Y et al. | — | 1994 | → |
| Effects of neuropeptide Y on the electrical properties of neurons. | Colmers WF et al. | — | 1994 | → |