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Full-Text Articles in Pharmacology, Toxicology and Environmental Health

Measuring Functional Brain Recovery In Regenerating Planarians By Assessing The Behavioral Response To The Cholinergic Compound Cytisine, Oné R. Pagán, Debra L. Baker, Sean Deats, Mary O'Brien, Rochelle Dymond, Gabriella Demichele Jan 2020

Measuring Functional Brain Recovery In Regenerating Planarians By Assessing The Behavioral Response To The Cholinergic Compound Cytisine, Oné R. Pagán, Debra L. Baker, Sean Deats, Mary O'Brien, Rochelle Dymond, Gabriella Demichele

Biology Faculty Publications

Planarians are traditional model invertebrates in regeneration and developmental biology research that also display a variety of quantifiable behaviors useful to screen for pharmacologically active compounds. One such behavior is the expression of seizure-like movements (pSLMs) induced by a variety of substances. Previous work from our laboratory showed that cocaine, but not nicotine, induced pSLMs in intact but not decapitated planarians. Interestingly, as decapitated planarians regenerated their heads, they gradually recovered their sensitivity to cocaine. These results suggested a method to assess planarian brain regeneration and a possible way of identifying compounds that could enhance or hold back brain regeneration. …


Cotinine Antagonizes The Behavioral Effects Of Nicotine Exposure In The Planarian Girardia Tigrina, Daniel J. Bach, Matthew Tenaglia, Debra L. Baker, Sean Deats, Erica Montgomery, Oné R. Pagán Oct 2016

Cotinine Antagonizes The Behavioral Effects Of Nicotine Exposure In The Planarian Girardia Tigrina, Daniel J. Bach, Matthew Tenaglia, Debra L. Baker, Sean Deats, Erica Montgomery, Oné R. Pagán

Biology Faculty Publications

Nicotine is one of the most addictive drugs abused by humans. Our laboratory and others have demonstrated that nicotine decreases motility and induces seizure-like behavior in planarians (pSLM, which are vigorous writhing and bending of the body) in a concentration-dependent manner. Nicotine also induces withdrawal-like behaviors in these worms. Cotinine is the major nicotine metabolite in humans, although it is not the final product of nicotine metabolism. Cotinine is mostly inactive in vertebrate nervous systems and is currently being explored as a molecule which possess most of nicotine’s beneficial effects and few of its undesirable ones. It is not known …


Planarians Require An Intact Brain To Behaviorally React To Cocaine, But Not To React To Nicotine, Oné R. Pagán, Sean Deats, Debra Baker, Erica Montgomery, Galia Wilk, Matthew Tenaglia, Joshua Semon Aug 2013

Planarians Require An Intact Brain To Behaviorally React To Cocaine, But Not To React To Nicotine, Oné R. Pagán, Sean Deats, Debra Baker, Erica Montgomery, Galia Wilk, Matthew Tenaglia, Joshua Semon

Biology Faculty Publications

Planarians possess a rudimentary brain with many features in common with vertebrate brains. They also display a remarkable capacity for tissue regeneration including the complete regeneration of the nervous system. Using the induction of planarian seizure-like movements (pSLMs) as a behavioral endpoint, we demonstrate that an intact nervous system is necessary for this organism to react to cocaine exposure, but not necessary to react to nicotine administration. Decapitated planarians (Girardia tigrina) display pSLMs indistinguishable from intact worms when exposed to nicotine, but cocaine-induced pSLMs are reduced by about 95% upon decapitation. Decapitated worms recover their normal sensitivity to cocaine within …


Planarians In Pharmacology: Parthenolide Is A Specific Behavioral Antagonist Of Cocaine In The Planarian Girardia Tigrina, Oné R. Pagán, Debra Baker, Sean Deats, Erica Montgomery, Matthew Tenaglia, Clinita Randolph, Dharini Kotturu, Christopher Tallarida, Daniel Bach, Galia Wilk, Scott Rawls, Robert B. Raffa Mar 2012

Planarians In Pharmacology: Parthenolide Is A Specific Behavioral Antagonist Of Cocaine In The Planarian Girardia Tigrina, Oné R. Pagán, Debra Baker, Sean Deats, Erica Montgomery, Matthew Tenaglia, Clinita Randolph, Dharini Kotturu, Christopher Tallarida, Daniel Bach, Galia Wilk, Scott Rawls, Robert B. Raffa

Biology Faculty Publications

Planarians are traditional animal models in developmental and regeneration biology. Recently, these organisms are arising as vertebrate-relevant animal models in neuropharmacology. Using an adaptation of published behavioral protocols, we have described the alleviation of cocaine-induced planarian seizure-like movements (pSLM) by a naturally-occurring sesquiterpene lactone, parthenolide. Interestingly, parthenolide does not prevent the expression of pSLM induced by amphetamines; in vertebrates, amphetamines interact with the same protein target as cocaine. Parthenolide is also unable to prevent pSLM elicited by the cholinergic compounds nicotine and cytisine or by the glutamatergic agents L- or D- glutamic acid or NMDA. Thus, we conclude that parthenolide …


Minimal Structural Requirements Of Alkyl Γ-Lactones Capable Of Antagonizing The Cocaine-Induced Motility Decrease In Planarians, Debra Baker, Sean Deats, Peter Boor, James Pruitt, Oné R. Pagán Nov 2011

Minimal Structural Requirements Of Alkyl Γ-Lactones Capable Of Antagonizing The Cocaine-Induced Motility Decrease In Planarians, Debra Baker, Sean Deats, Peter Boor, James Pruitt, Oné R. Pagán

Biology Faculty Publications

We recently reported that the natural cyclic lactone, parthenolide, and related analogs prevent the expression of behavioral effects induced by cocaine in planarians and that parthenolide’s γ-lactone ring is required for this effect. In the present work, we tested a series of alkyl γ-lactones with varying chain length (1–8 carbons) to determine their ability to antagonize the planarian motility decrease induced by 200 μM cocaine. Alkyl lactones with up to a 4-carbon alkyl chain did not affect planarian motility or antagonized the cocaine-induced motility decrease; only the compound γ-nonalactone (a γ-lactone with a 5-carbon chain) was able to prevent the …


Parthenolide Blocks Cocaine’S Effect On Spontaneous Firing Activity Of Dopaminergic Neurons In The Ventral Tegmental Area, David Schwarz, Damaris Bloom, Rocío Castro, Oné R. Pagán, C. A. Jiménez-Rivera Mar 2011

Parthenolide Blocks Cocaine’S Effect On Spontaneous Firing Activity Of Dopaminergic Neurons In The Ventral Tegmental Area, David Schwarz, Damaris Bloom, Rocío Castro, Oné R. Pagán, C. A. Jiménez-Rivera

Biology Faculty Publications

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 cocaine’s locomotion effects in a planarian animal model (Pagán 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 …


Actions Of Octocoral And Tobacco Cembranoids On Nicotinic Receptors, P. A. Ferchmin, Oné R. Pagán, Henning Ulrich, Ada C. Szeto, Richard M. Hann, Vesna A. Eterović Dec 2009

Actions Of Octocoral And Tobacco Cembranoids On Nicotinic Receptors, P. A. Ferchmin, Oné R. Pagán, Henning Ulrich, Ada C. Szeto, Richard M. Hann, Vesna A. Eterović

Biology Faculty Publications

Nicotinic acetylcholine receptors (AChRs) are pentameric proteins that form agonist-gated cation channels through the plasma membrane. AChR agonists and antagonists are potential candidates for the treatment of neurodegenerative diseases. Cembranoids are naturally occurring diterpenoids that contain a 14-carbon ring. These diterpenoids interact with AChRs in complex ways: as irreversible inhibitors at the agonist sites, as noncompetitive inhibitors, or as positive modulators, but no cembranoid was ever shown to have agonistic activity on AChRs. The cembranoid eupalmerin acetate displays positive modulation of agonist-induced currents in the muscle-type AChR and in the related gamma-aminobutyric acid (GABA) type A receptor. Moreover, cembranoids display …


A Cembranoid From Tobacco Prevents The Expression Of Nicotineinduced Withdrawal Behavior In Planarian Worms, Oné R. Pagán, Amanda L. Rowlands, Angela L. Fattore, Tamara Coudron, Kimberly R. Urban, Apurva H. Bidja, Vesna A. Eterović Aug 2009

A Cembranoid From Tobacco Prevents The Expression Of Nicotineinduced Withdrawal Behavior In Planarian Worms, Oné R. Pagán, Amanda L. Rowlands, Angela L. Fattore, Tamara Coudron, Kimberly R. Urban, Apurva H. Bidja, Vesna A. Eterović

Biology Faculty Publications

Using an adaptation of published behavioral protocols, we determined that acute exposure to the cholinergic compounds nicotine and carbamylcholine decreased planarian motility in a concentration-dependent manner. A tobacco cembranoid (1S,2E,4R,6R,7E,11E)-cembra-2,7,11- triene-4,6-diol (4R-cembranoid), also decreased planarian motility. Experiments in the presence of 1 μM 4R-cembranoid did increase the IC50 for nicotine- but not carbamylcholine-induced decrease in planarian motility. When planarians were exposed for 24 h to either nicotine or carbamylcholine at concentrations near their respective IC50 values and then transferred to plain media, nicotineexposed, but not carbamylcholine- or cembranoid-exposed worms displayed withdrawal-like distress behaviors. In experiments where planarians were pre-exposed to …