Planaria raffa robert b rawls scott m. Agmatine: Identification and inhibition of methamphetamine, kappa opioid, and cannabinoid withdrawal in planarians 2019-01-25

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Pharmacology

planaria raffa robert b rawls scott m

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 cocaine-induced behavioral patterns, while alkyl lactones with longer carbon chains failed to prevent the cocaine-induced effects. This synergy, here analyzed with the latest nonlinear isobolographic methodology, is now quantitatively established for the first time. The major excitatory neurotransmitters in the mammalian central nervous system are glutamate and aspartate. More interesting readouts include morphological aberrations, body distortions or changes in behavior, which may be specific to certain chemical classes Passarelli et al. Together with changes in 2 nd -messenger levels e. Planarian hyperactivity was quantified as the number of C-like hyperkinesias during a 1-min drug exposure. For combined exposure, variable cocaine concentrations 0.

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Publications Authored by Scott M Rawls

planaria raffa robert b rawls scott m

Effects of co-treatment of scopolamine and galantamine on memory retention in planaria via classical Pavlovian conditioning experiments showed that galantamine 0. Thus, they are the lowest form of animal that would display relevant neurotoxicity. It offers a unique visual approach to learning the basic principles of pharmacology - providing the most authoritative and broadest possible coverage of both the basic science and the clinical applications of pharmacology in a manner that is both scientifically rigorous and enjoyable. These effects were antagonized by coexposure to cannabinoid or opioid receptor antagonists. Nicotine-treated planarians withdrawn from the drug for 3 days before being challenged with nicotine displayed behavioral sensitization at low concentrations 0. Recent efforts to elucidate the mechanisms of action of several anti-inflammatory herbs have focused on a class of compounds, sesquiterpene lactones, which are believed to be the active components of these herbal medicines. Feverfew has been traditionally used as a herbal medicine for the treatment of fever, arthritis, and migraine in Asia and Europe for centuries.

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Planaria : a model for drug action and abuse

planaria raffa robert b rawls scott m

Moreover, a variety of experimental studies characterized specific behavioral patterns of these animals following the exposure to drugs acting on neural transmission. The dopamine D2 receptor antagonist sulpiride decreases the spontaneous locomotor activity of Planaria in an enantiomeric-selective and dose-dependent manner. Wild-type locomotion in confinement was quantified using a wide set of parameters, and the influences of intrinsic intra-worm versus inter-worm variability on our measurements was studied. This compound can elicit various physiological effects in both vertebrates and invertebrates. Planarians are a desirable model for these studies for several reasons, including cephalization cephalic ganglia and bilateral spinal processes , primitive neurotransmitter systems dopaminergic, serotonergic, opioidergic, etc. General activity was not affected. The results are discussed adopting an evolutionary-comparative approach.

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Planaria : a model for drug action and abuse (eBook, 2008) [getu.com]

planaria raffa robert b rawls scott m

Although many drug abusers engage in dpolydrugT abuse, little is currently known about the development of physical dependence or withdrawal following multidrug use. Carbamazepine and oxcarbazepine, iminodibenzyl derivatives, exhibit anticonvulsive effects mediated mainly through the inactivation of voltage-gated sodium channels. Arginine, the metabolic precursor to agmatine, was ineffective. We developed a rapid and efficient method for the extraction and measurement of these amino acids in Planaria--a valuable model for mammalian processes because of their simple, centralized nervous system and similar neurotransmitter systems. Nicotine is one of the world's most addictive substances and the primary reason that humans inhale tobacco smoke. The effects of reuptake inhibitors on cocaine activity were also studied. It has been suggested that over the first few weeks of withdrawal from cocaine, human addicts become sensitized to drug-associated environmental cues that act as external stimuli for craving, although the evidence for this is inconsistent.

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kappa

planaria raffa robert b rawls scott m

There are several hundred planarian species Oviedo et al. In Experiment 3, pre-training of one of the elements before compound conditioning resulted in blocking of learning about the other element. The motor system of Dugesia gonocephala shows a striking similarity with the extrapyramidal system of high vertebrates and of man with the evidence of correlations between dopaminergic and cholinergic neurons. Classical data suggest that they may also be capable of long-term memory. Besides, it might be anticipated that this model, if correctly used, can display interesting perspectives also in neuroendocrinological investigations. The dish was placed over paper with gridlines spaced 0.

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Pharmacology

planaria raffa robert b rawls scott m

However, despite much indirect evidence, we lacked direct evidence of a receptor- or carrier-mediated effect. We then used this new system to train flatworms in an environmental familiarization protocol. These data provide pharmacologic evidence of a kappa-opioid receptor-mediated withdrawal phenomenon and neuroadaptation to a pharmacologic stimulus adaptations in transduction mechanisms in this model. We demonstrated here that planarians also display withdrawal responses to a natural reward sucrose that are spontaneous and do not require precipitation with a receptor antagonist. This response is inhibited by a D2 selective blocking agent.

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Planaria; a model for drug action and abuse.

planaria raffa robert b rawls scott m

The peak cocaine effect was observed following a 24-h exposure. For the antagonist experiments, four conditions were studied: water alone, agonist alone, antagonist alone, and agonist plus antagonist. 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. Since the postulated mechanisms of action of the sulfamate-substituted monosaccharide antiepileptic drug topiramate include inhibition of glutamate-activated ion channels, we tested the hypothesis that topiramate would inhibit glutamate-induced paroxysms in our model. Planaria's nervous system presents anatomical e. Planarians are being rediscovered as a very useful animal model to study abused drugs. Planarians exposed to nicotine 0.

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Planaria : a model for drug action and abuse

planaria raffa robert b rawls scott m

Planaria were placed in a small petri dish containing 3 mL of spring water on top of 0. Neurosci Biobehav Rev 2017 06 28;77:209-218. A median concentration 1 % produced the greatest shift whereas relatively lower 0. These data provide pharmacologic evidence of a κ-opioid receptor-mediated withdrawal phenomenon and neuroadaptation to a pharmacologic stimulus adaptations in transduction mechanisms in this model. The chosen range covered 0.

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Pharmacology

planaria raffa robert b rawls scott m

Time spent in the non-preferred environment was determined posttest , and a preference score was calculated as the difference between the posttest and pretest times. Planarian motility and stereotypy C-shape hyperkinesias were quantified following acute nicotine exposure. The results substantiate conclusions concerning the phylogenesis of hormone receptors. Two studies demonstrated that acute nicotine exposure alters stereotypical activity and motility and produces quantifiable withdrawal effects following cessation of exposure Buttarelli et al. Here, we demonstrate for the first time using a planarian model that ceftriaxone attenuates both the development of physical dependence and abstinence-induced withdrawal from cocaine, amphetamine, methamphetamine, and a benzodiazepine clorazepate in a concentration-related manner.

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