Abstract
Chronic cocaine administration leads to catecholamine reuptake inhibition which enhances reward and motivational behaviors. Ventral Tegmental Area dopaminergic (VTA DA) neuronal firing is associated with changes in reward predictive signals. Acute cocaine injections inhibit putative VTA DA cell firing in vertebrates. Parthenolide, a compound isolated from the feverfew plant (Tanacetum parthenium), has been shown to substantially inhibit cocaines locomotion effects in a planarian animal model (Pagan et al., 2008). Here we investigated the effects of parthenolide on the spontaneous firing activity of putative VTA DA neurons in anesthetized male rats (250-300g). Single-unit recordings were analyzed after intravenous (i.v.) parthenolide administration followed by 1mg/kg i.v. cocaine injection. Results showed that parthenolide at 0.125 mg/kg and 0.250mg/kg significantly blocked cocaines inhibitory effect on DA neuronal firing rate and bursting activity (p < 0.05, two way ANOVA). We propose that parthenolide might inhibit cocaines effects on VTA DA neurons via its interaction with a common binding site at monoamine transporters. It is suggested that parthenolide could have a potential use as an overdose antidote or therapeutic agent to cocaine intoxication.
Keywords: Cocaine, parthenolide, ventral tegmental, dopamine, firing activity, Fluoxetine, Catechol amine reuptake, DA Neurons, Cocaine Sensitzation, ACTH
Current Neuropharmacology
Title: Parthenolide Blocks Cocaines Effect on Spontaneous Firing Activity of Dopaminergic Neurons in the Ventral Tegmental Area
Volume: 9 Issue: 1
Author(s): David Schwarz, Damaris Bloom, Rocio Castro, One R. Pagan and C. A. Jimenez-Rivera
Affiliation:
Keywords: Cocaine, parthenolide, ventral tegmental, dopamine, firing activity, Fluoxetine, Catechol amine reuptake, DA Neurons, Cocaine Sensitzation, ACTH
Abstract: Chronic cocaine administration leads to catecholamine reuptake inhibition which enhances reward and motivational behaviors. Ventral Tegmental Area dopaminergic (VTA DA) neuronal firing is associated with changes in reward predictive signals. Acute cocaine injections inhibit putative VTA DA cell firing in vertebrates. Parthenolide, a compound isolated from the feverfew plant (Tanacetum parthenium), has been shown to substantially inhibit cocaines locomotion effects in a planarian animal model (Pagan et al., 2008). Here we investigated the effects of parthenolide on the spontaneous firing activity of putative VTA DA neurons in anesthetized male rats (250-300g). Single-unit recordings were analyzed after intravenous (i.v.) parthenolide administration followed by 1mg/kg i.v. cocaine injection. Results showed that parthenolide at 0.125 mg/kg and 0.250mg/kg significantly blocked cocaines inhibitory effect on DA neuronal firing rate and bursting activity (p < 0.05, two way ANOVA). We propose that parthenolide might inhibit cocaines effects on VTA DA neurons via its interaction with a common binding site at monoamine transporters. It is suggested that parthenolide could have a potential use as an overdose antidote or therapeutic agent to cocaine intoxication.
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Schwarz David, Bloom Damaris, Castro Rocio, R. Pagan One and A. Jimenez-Rivera C., Parthenolide Blocks Cocaines Effect on Spontaneous Firing Activity of Dopaminergic Neurons in the Ventral Tegmental Area, Current Neuropharmacology 2011; 9 (1) . https://dx.doi.org/10.2174/157015911795017010
DOI https://dx.doi.org/10.2174/157015911795017010 |
Print ISSN 1570-159X |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6190 |
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