Cocaine and κ-opioid withdrawal in Planaria blocked by d-, but not l-, glucose

Umeda, Sumiyo; Stagliano, Gregory W.; Raffa, Robert B.

doi:10.1016/j.brainres.2004.05.057

Cited by 19 publications

(20 citation statements)

References 15 publications

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“…But, our data do suggest that at low concentrations, glucose does provide a supportive effect to guarana stimulation over longer periods. These data are in line with published reports suggesting that glucose can support the effect of stimulants in the planarian model [48]. Conversely, our combinations of glucose and caffeine did not result in an increase of planarian motility at either time-point examined (Fig 6) providing further evidence of stimulant properties in guarana that are indeed different from those of caffeine.…”

Section: Discussionsupporting

confidence: 92%

Guarana Provides Additional Stimulation over Caffeine Alone in the Planarian Model

et al. 2015

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The stimulant effect of energy drinks is primarily attributed to the caffeine they contain. Many energy drinks also contain other ingredients that might enhance the tonic effects of these caffeinated beverages. One of these additives is guarana. Guarana is a climbing plant native to the Amazon whose seeds contain approximately four times the amount of caffeine found in coffee beans. The mix of other natural chemicals contained in guarana seeds is thought to heighten the stimulant effects of guarana over caffeine alone. Yet, despite the growing use of guarana as an additive in energy drinks, and a burgeoning market for it as a nutritional supplement, the science examining guarana and how it affects other dietary ingredients is lacking. To appreciate the stimulant effects of guarana and other natural products, a straightforward model to investigate their physiological properties is needed. The planarian provides such a system. The locomotor activity and convulsive response of planarians with substance exposure has been shown to provide an excellent system to measure the effects of drug stimulation, addiction and withdrawal. To gauge the stimulant effects of guarana we studied how it altered the locomotor activity of the planarian species Dugesia tigrina. We report evidence that guarana seeds provide additional stimulation over caffeine alone, and document the changes to this stimulation in the context of both caffeine and glucose.

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Section: Discussionsupporting

confidence: 92%

Guarana Provides Additional Stimulation over Caffeine Alone in the Planarian Model

et al. 2015

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“…Specifically, it is difficult to quantify a tangible withdrawal behavior following the spontaneous discontinuation of some drugs. We therefore used planarians, a substitute that we have used extensively to demonstrate withdrawal to a variety of drugs (Raffa and Desai, 2005;Raffa and Martley, 2005;Raffa and Valdez, 2001;Raffa et al, 2000Raffa et al, , 2003Rawls et al, 2006bRawls et al, , 2007bUmeda et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…One of the reasons is the difficulty in quantifying a withdrawal syndrome to some of these drugs in mammals (Cox et al, 2004;Lago and Kosten, 1994;McGregor et al, 2005;Segal and Kuczenski, 2006;Segal et al, 2005;Takamatsu et al, 2006). An alternative to mammals is planarians, a type of flatworm that displays withdrawal to cocaine, cannabinoid agonists, j-opioid agonists, amphetamines, and benzodiazepines (Raffa and Desai, 2005;Raffa and Martley, 2005;Raffa and Valdez, 2001;Raffa et al, 2000Raffa et al, , 2003Raffa et al, , 2006Raffa et al, , 2007Rawls et al, 2006bRawls et al, , 2007aUmeda et al, 2004). The withdrawal is manifested as a decrease in spontaneous locomotor activity following the discontinuation of drug exposure (Raffa and Valdez, 2001;Raffa et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…Planarians do not display withdrawal to opioid antagonists, glutamate antagonists, nitric oxide synthase blockers, and vanilloids (Raffa et al, 2003(Raffa et al, , 2006(Raffa et al, , 2007Rawls et al, 2006bRawls et al, , 2007b. The cause of the reduced locomotor activity is not related to factors such as osmolarity or pH (Umeda et al, 2004). It is also important to note that planarians contain a centralized nervous system, utilize mammalian-like neurotransmitters (e.g., dopamine (DA), 5-HT, glutamate, GABA, and endogenous opioids), and display complex behavioral adaptation, including learning, memory, and drug preference (Algeri et al, 1983;Eriksson and Panula, 1994;Kimmel and Garrigan, 1973;Kusayama and Watanabe, 2000;Newmark and Sanchez Alvarado, 2002;Rawls et al, 2006a;Umeda et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Agmatine: Identification and inhibition of methamphetamine, kappa opioid, and cannabinoid withdrawal in planarians

Gerber

Ding

Roth

et al. 2008

Synapse

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Agmatine blocks morphine physical dependence in mammals, but its effects on withdrawal signs caused by other abused drugs have been less studied. One of the reasons is that withdrawal to some of these drugs is difficult to quantify in mammals. An alternative to mammals is planarians, a type of flatworm. Planarians possess mammalian-like neurotransmitters and display withdrawal from amphetamines, benzodiazepines, cannabinoids, cocaine, and opioids. The withdrawal is manifested as a reduction in locomotor behavior following discontinuation of drug exposure. In the present study, our goal was to identify agmatine in planarians and to determine if planarians exposed to agmatine display withdrawal to methamphetamine, a cannabinoid receptor agonist (WIN 55,212-2), or a kappa-opioid receptor agonist (U-50,488H). Neurochemical experiments revealed that the concentration of agmatine in planarians was 185 +/- 33.7 pmol per mg of planarian weight (dry weight). In behavioral experiments, withdrawal (i.e., reduced locomotor activity) was observed when planarians exposed to each drug (10 microM) for 60 min were placed into water. The withdrawal was attenuated when methamphetamine- or U-50,488H-exposed planarians were tested in agmatine (100 microM). Withdrawal was inhibited similarly when planarians coexposed to agmatine (100 microM) plus methamphetamine (10 microM), WIN 55,212-2 (10 microM), or U-50,488H (10 microM) were tested in water. Arginine, the metabolic precursor to agmatine, was ineffective. Our results identify endogenous agmatine in planarians and demonstrate that agmatine exposure blocks withdrawal to three different drugs in planarians. This suggests that a change in agmatine signaling is a common mechanism in the withdrawal caused by these drugs, at least in planarians.

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“…We here report a convenient and facile non-mammalian model for in vivo demonstration and quantitative assessment of DOPA decarboxylase or an equivalent enzyme activity in a species with primitive nervous system and mammalian-analogous neurotransmitter and 2nd messenger systems [17][18][19][20][21][22][23][24][25][26]. The model is useful for the study of drug action and for physiological aspects of drug abuse [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43].…”

Section: Introductionmentioning

confidence: 99%

Potential of a planarian model to study certain aspects of anti-Parkinsonism drugs

B.¹,

Jeff²,

S.³

et al. 2013

APD

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We previously created and investigated a planarian model for the study of drug action, abuse, physical dependence, receptor affinity, the toxicity of heavy metals in wastewater, and seizures. For the present pilot study, we investigated the possibility that this model might be useful for studying certain aspects of drugs used in treatment of Parkinson disease. For the first step, we were interested in finding an in vivo metric for the inhibition of L-DOPA by an inhibitor of DOPA decarboxylase. The direct clinical relevance of the endpoint was of secondary concern during this preliminary phase of model development. Two metrics were explored: L-DOPA-induced inhibition of motility (locomotor velocity) and dopamine-mediated toxicity, which was quantified using a Kaplan-Meier survival curve. L-DOPA produced both dose-and timerelated toxicity. The water-soluble DOPA decarboxylase inhibitor benserazide dose-dependently inhibited the effect of L-DOPA, as manifested by a leftward shift in the Kaplan-Meier curve. Additional work was initiated using the more sensitive and a graded metric of spontaneous locomotor velocity. The encouraging results of this pilot study suggest that: 1) planarians contain DOPA decarboxylase or an equivalent enzyme, and 2) the planarian model might be useful for the study of certain aspects of anti-Parkinsonism pharmacotherapy.

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Cocaine and κ-opioid withdrawal in Planaria blocked by d-, but not l-, glucose

Cited by 19 publications

References 15 publications

Guarana Provides Additional Stimulation over Caffeine Alone in the Planarian Model

Guarana Provides Additional Stimulation over Caffeine Alone in the Planarian Model

Agmatine: Identification and inhibition of methamphetamine, kappa opioid, and cannabinoid withdrawal in planarians

Potential of a planarian model to study certain aspects of anti-Parkinsonism drugs

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