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Scott Rawls, PhD
Associate Professor, Pharmacology
Associate Professor, Center for Substance Abuse Research
Telephone: 215-707-4942
Fax: 215-707-6661
Email:
scott.rawls@temple.edu
Department of Pharmacology
Center for Substance Abuse Research
BS, Chemistry, East Carolina University, Greenville, NC, 1990\
PhD, East Carolina University School of Medicine, Greenville, NC, 1999
NIDA Postdoctoral Fellowship, Temple University School of Medicine, Philadelphia, PA, 2000-2002
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Dr. Rawls’ laboratory uses vertebrate (rats, mice) and invertebrate (planarians) models to investigate the pharmacology of drugs of abuse such as cocaine, amphetamines, and opioids. Delineating a role for glutamate systems, in particular glutamate transporters, in drug addiction is the major focus of the laboratory. Recent work has been directed toward investigating glutamate transporter subtype 1 (GLT-1) biology and the effects of GLT-1 transporter activation in animal models of glutamate-related diseases. Antibiotics containing a β-lactam core (ceftriaxone, penicillin) are the only pharmaceuticals known to activate GLT-1 transporters. Dr. Rawls’ laboratory was awarded a NIH RC1 challenge grant to investigate the efficacy of β-lactam compounds in preclinical assays that model aspects of cocaine and opioid addiction. Important findings are that ceftriaxone inhibits the reinforcing properties of cocaine in a mouse model of self-administration, attenuates psychostimulant-induced locomotor activation in rats and mice, prevents morphine analgesic tolerance and physical dependence in rats, and restores cocaine-induced deficits in limbic white matter protein expression. Another key finding is that the β-lactamase inhibitor clavulanic acid – a ceftriaxone analog that retains the β-lactam core required for GLT-1 activity but possesses a more patient-friendly profile (enhanced brain penetrability, minimal antibacterial activity, oral activity) – displays a pharmacological and neurochemical profile resembling ceftriaxone. Efforts proposing to test the efficacy of clavulanic acid in cocaine-abusing human populations are currently underway.
A more recent focus has been directed toward defining the neuropharmacological profile of psychoactive bath salts (PABS). PABS are a dangerous street drug in the United States and Europe comprised of multiple ingredients that possess abuse liability and toxicity. A principal component of PABS is mephedrone (4-methylmethcathinone), a synthetic compound that displays structural similarities to cathinone and amphetamine. Mephedrone use is increasing in the United States, where the American Association of Poison Control Centers reported almost a 20-fold rise in mephedrone exposures from 2010 to 2011. Dr. Rawls’ laboratory has been at the forefront of investigating the neurochemical, behavioral, and cellular effects of mephedrone and determining how its abuse liability and neuropharmacological profile compare with established drugs of abuse such as methamphetamine, ecstasy, and cocaine. Early evidence suggests that mephedrone produces rewarding properties in rats and dopamine-sensitive locomotor activation in rats and invertebrates. Self-administration and drug discrimination studies are planned to assess the reinforcing efficacy and abuse liability of mephedrone relative to more established drugs of abuse.
The laboratory also uses invertebrate (planarian) assays to screen compounds for anti-addictive and anti-seizure properties and provide an in vivo model to teach the science of addiction to elementary, middle, and high school students. Planarians possess a centralized nervous system which some consider the simplest ‘brain’ and mammalian-like neurotransmitters (glutamate, GABA, dopamine, serotonin, opioids, acetylcholine). In collaboration with Dr. Robert Raffa, our laboratory has demonstrated that planarians display reproducible and quantifiable mammalian-like responses when exposed to abused drugs (e.g. motor activation, stereotypy, sensitization, conditioned place preference).
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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)
23415661. Zhang C, Tallarida CS, Raffa RB, Rawls SM, Sucrose produces withdrawal and dopamine-sensitive reinforcing effects in planarians. Physiol Behav 112-113:(8-13)2013 Mar 15
23031254. Kovalevich J, Corley G, Yen W, Rawls SM, Langford D, Cocaine-induced loss of white matter proteins in the adult mouse nucleus accumbens is attenuated by administration of a ß-lactam antibiotic during cocaine withdrawal. Am J Pathol 181:6(1921-7)2012 Dec
22877698. Owaisat S, Raffa RB, Rawls SM, In vivo comparison of harmine efficacy against psychostimulants: preferential inhibition of the cocaine response through a glutamatergic mechanism. Neurosci Lett 525:1(12-6)2012 Sep 6
22652295. Lisek R, Xu W, Yuvasheva E, Chiu YT, Reitz AB, Liu-Chen LY, Rawls SM, Mephedrone ('bath salt') elicits conditioned place preference and dopamine-sensitive motor activation. Drug Alcohol Depend 126:1-2(257-62)2012 Nov 1
22300981. Ramoz L, Lodi S, Bhatt P, Reitz AB, Tallarida C, Tallarida RJ, Raffa RB, Rawls SM, Mephedrone ("bath salt") pharmacology: insights from invertebrates. Neuroscience 208:(79-84)2012 Apr 19
22300446. Kovalevich J, Corley G, Yen W, Kim J, Rawls SM, Langford D, Cocaine decreases expression of neurogranin via alterations in thyroid receptor/retinoid X receptor signaling. J Neurochem 121:2(302-13)2012 Apr
22027514. Schroeder JA, Quick KF, Landry PM, Rawls SM, Glutamate transporter activation enhances nicotine antinociception and attenuates nicotine analgesic tolerance. Neuroreport 22:18(970-3)2011 Dec 21
21850438. Tallarida C, Song K, Raffa RB, Rawls SM, Glutamate carboxypeptidase II (GCPII) inhibitor displays anti-glutamate and anti-cocaine effects in an invertebrate assay. Amino Acids 42:6(2521-4)2012 Jun
21622235. Rawls SM, Benamar K, Effects of opioids, cannabinoids, and vanilloids on body temperature. Front Biosci (Schol Ed) 3:(822-45)2011 Jun 1
21543969. Ward SJ, Rasmussen BA, Corley G, Henry C, Kim JK, Walker EA, Rawls SM, Beta-lactam antibiotic decreases acquisition of and motivation to respond for cocaine, but not sweet food, in C57Bl/6 mice. Behav Pharmacol 22:4(370-3)2011 Aug
21530106. Rawls SM, Patil T, Tallarida CS, Baron S, Kim M, Song K, Ward S, Raffa RB, Nicotine behavioral pharmacology: clues from planarians. Drug Alcohol Depend 118:2-3(274-9)2011 Nov 1
21524862. Rasmussen B, Unterwald EM, Rawls SM, Glutamate transporter subtype 1 (GLT-1) activator ceftriaxone attenuates amphetamine-induced hyperactivity and behavioral sensitization in rats. Drug Alcohol Depend 118:2-3(484-8)2011 Nov 1
21315691. Kim J, Cowan A, Lisek R, Raymondi N, Rosenthal A, Hirsch DD, Rawls SM, Icilin-evoked behavioral stimulation is attenuated by alpha2-adrenoceptor activation. Brain Res 1384:(110-7)2011 Apr 12
20863783. Raffa RB, Finno KE, Tallarida CS, Rawls SM, Topiramate-antagonism of L-glutamate-induced paroxysms in planarians. Eur J Pharmacol 649:1-3(150-3)2010 Dec 15
20709144. Rawls SM, Shah H, Ayoub G, Raffa RB, 5-HT(1A)-like receptor activation inhibits abstinence-induced methamphetamine withdrawal in planarians. Neurosci Lett 484:2(113-7)2010 Oct 29
20708699. Vyas CA, Rawls SM, Raffa RB, Shackman JG, Glutamate and aspartate measurements in individual planaria by rapid capillary electrophoresis. J Pharmacol Toxicol Methods 63:1(119-22)2011 Jan-Feb
20600649. Rawls SM, Karaca F, Madhani I, Bhojani V, Martinez RL, Abou-Gharbia M, Raffa RB, ß-lactamase inhibitors display anti-seizure properties in an invertebrate assay. Neuroscience 169:4(1800-4)2010 Sep 15
20512030. Rawls SM, Patil T, Yuvasheva E, Raffa RB, First evidence that drugs of abuse produce behavioral sensitization and cross sensitization in planarians. Behav Pharmacol 21:4(301-13)2010 Jul
20383795. Rasmussen BA, Baron DA, Kim JK, Unterwald EM, Rawls SM, ß-Lactam antibiotic produces a sustained reduction in extracellular glutamate in the nucleus accumbens of rats. Amino Acids 40:2(761-4)2011 Feb
20215965. Rawls SM, Baron DA, Kim J, beta-Lactam antibiotic inhibits development of morphine physical dependence in rats. Behav Pharmacol 21:2(161-4)2010 Mar
20004063. Rawls SM, Zielinski M, Patel H, Sacavage S, Baron DA, Patel D, Beta-lactam antibiotic reduces morphine analgesic tolerance in rats through GLT-1 transporter activation. Drug Alcohol Depend 107:2-3(261-3)2010 Mar 1
19879869. Rasmussen BA, Unterwald EM, Kim JK, Rawls SM, Methanandamide blocks amphetamine-induced behavioral sensitization in rats. Eur J Pharmacol 627:1-3(150-5)2010 Feb 10
19575185. Ward SJ, Lefever TW, Rawls SM, Whiteside GT, Walker EA, Age-dependent effects of the cannabinoid CB1 antagonist SR141716A on food intake, body weight change, and pruritus in rats. Psychopharmacology (Berl) 206:1(155-65)2009 Sep
19538988. Aggarwal S, Shavalian B, Kim E, Rawls SM, Agmatine enhances cannabinoid action in the hot-plate assay of thermal nociception. Pharmacol Biochem Behav 93:4(426-32)2009 Oct
19536110. Wu HM, Tzeng NS, Qian L, Wei SJ, Hu X, Chen SH, Rawls SM, Flood P, Hong JS, Lu RB, Novel neuroprotective mechanisms of memantine: increase in neurotrophic factor release from astroglia and anti-inflammation by preventing microglial activation. Neuropsychopharmacology 34:10(2344-57)2009 Sep
19463266. Corley G, Rawls SM, Opioid, cannabinoid CB1 and NOP receptors do not mediate APAP-induced hypothermia in rats. Pharmacol Biochem Behav 92:3(503-7)2009 May
19447129. Rawls SM, Thomas T, Adeola M, Patil T, Raymondi N, Poles A, Loo M, Raffa RB, Topiramate antagonizes NMDA- and AMPA-induced seizure-like activity in planarians. Pharmacol Biochem Behav 93:4(363-7)2009 Oct
19401177. Rasmussen BA, Kim E, Unterwald EM, Rawls SM, Methanandamide attenuates cocaine-induced hyperthermia in rats by a cannabinoid CB(1)-dopamine D(2) receptor mechanism. Brain Res :()2009 Jan 17
19248800. Werkheiser J, Cowan A, Gomez T, Henry C, Parekh S, Chau S, Baron DA, Rawls SM, Icilin-induced wet-dog shakes in rats are dependent on NMDA receptor activation and nitric oxide production. Pharmacol Biochem Behav 92:3(543-8)2009 May
18792993. Rawls SM, Gerber K, Ding Z, Roth C, Raffa RB, Agmatine: identification and inhibition of methamphetamine, kappa opioid, and cannabinoid withdrawal in planarians. Synapse 62:12(927-34)2008 Dec
18644397. Rawls SM, Robinson W, Patel S, Baron A, Beta-lactam antibiotic prevents tolerance to the hypothermic effect of a kappa opioid receptor agonist. Neuropharmacology 55:5(865-70)2008 Oct
18511196. Sacavage S, Patel H, Zielinski M, Acker J, Phillips AG, Raffa RB, Rawls SM, Withdrawal-like behavior in planarians is dependent on drug exposure duration. Neurosci Lett 439:1(84-8)2008 Jul 4
18479746. Rawls SM, Baron S, Ding Z, Roth C, Zaveri N, Raffa RB, Nociceptin attenuates methamphetamine abstinence-induced withdrawal-like behavior in planarians. Neuropeptides 42:3(229-37)2008 Jun
18342307. Rawls SM, Cavallo F, Capasso A, Ding Z, Raffa RB, The beta-lactam antibiotic ceftriaxone inhibits physical dependence and abstinence-induced withdrawal from cocaine, amphetamine, methamphetamine, and clorazepate in planarians. Eur J Pharmacol 584:2-3(278-84)2008 Apr 28
18178175. Raffa RB, Stagliano GW, Ross G, Powell JA, Phillips AG, Ding Z, Rawls SM, The kappa-opioid receptor antagonist nor-BNI inhibits cocaine and amphetamine, but not cannabinoid (WIN 52212-2), abstinence-induced withdrawal in planarians: an instance of 'pharmacologic congruence'. Brain Res 1193:(51-6)2008 Feb 8
18155835. Ding Z, Cowan A, Rawls SM, 5-HT reuptake and 5-HT2 receptors modulate capsaicin-evoked hypothermia in rats. Neurosci Lett 430:3(191-6)2008 Jan 17
18089845. Wang Y, Chen Y, Xu W, Lee DY, Ma Z, Rawls SM, Cowan A, Liu-Chen LY, 2-Methoxymethyl-salvinorin B is a potent kappa opioid receptor agonist with longer lasting action in vivo than salvinorin A. J Pharmacol Exp Ther 324:3(1073-83)2008 Mar
17976579. Ding Z, Gomez T, Werkheiser JL, Cowan A, Rawls SM, Icilin induces a hyperthermia in rats that is dependent on nitric oxide production and NMDA receptor activation. Eur J Pharmacol 578:2-3(201-8)2008 Jan 14
17765220. Rawls SM, Gomez T, Ding Z, Raffa RB, Differential behavioral effect of the TRPM8/TRPA1 channel agonist icilin (AG-3-5). Eur J Pharmacol 575:1-3(103-4)2007 Dec 1
17592517. Rawls SM, Tallarida R, Robinson W, Amin M, The beta-lactam antibiotic, ceftriaxone, attenuates morphine-evoked hyperthermia in rats. Br J Pharmacol 151:7(1095-102)2007 Aug
17512052. Rawls SM, Schroeder JA, Ding Z, Rodriguez T, Zaveri N, NOP receptor antagonist, JTC-801, blocks cannabinoid-evoked hypothermia in rats. Neuropeptides 41:4(239-47)2007 Aug
17376409. Rawls SM, Amin M, Zisk J, Agmatine blocks morphine-evoked hyperthermia in rats. Brain Res 1147:(89-94)2007 May 25
17306870. Rawls SM, Gomez T, Raffa RB, An NMDA antagonist (LY 235959) attenuates abstinence-induced withdrawal of planarians following acute exposure to a cannabinoid agonist (WIN 55212-2). Pharmacol Biochem Behav 86:3(499-504)2007 Mar
17150231. Werkheiser JL, Rawls SM, Cowan A, Nalfurafine, the kappa opioid agonist, inhibits icilin-induced wet-dog shakes in rats and antagonizes glutamate release in the dorsal striatum. Neuropharmacology 52:3(925-30)2007 Mar
17109846. Rawls SM, Tallarida RJ, Zisk J, Agmatine and a cannabinoid agonist, WIN 55212-2, interact to produce a hypothermic synergy. Eur J Pharmacol 553:1-3(89-98)2006 Dec 28
17018247. Ding Z, Cowan A, Tallarida R, Rawls SM, Capsaicin and nitric oxide synthase inhibitor interact to evoke a hypothermic synergy. Neurosci Lett 409:1(41-6)2006 Nov 27
16945367. Werkheiser JL, Rawls SM, Cowan A, Mu and kappa opioid receptor agonists antagonize icilin-induced wet-dog shaking in rats. Eur J Pharmacol 547:1-3(101-5)2006 Oct 10
16782070. Rawls SM, Rodriguez T, Baron DA, Raffa RB, A nitric oxide synthase inhibitor (L-NAME) attenuates abstinence-induced withdrawal from both cocaine and a cannabinoid agonist (WIN 55212-2) in Planaria. Brain Res 1099:1(82-7)2006 Jul 12
16647109. Rawls SM, Ding Z, Cowan A, Role of TRPV1 and cannabinoid CB1 receptors in AM 404-evoked hypothermia in rats. Pharmacol Biochem Behav 83:4(508-16)2006 Apr
16622598. Werkheiser JL, Rawls SM, Cowan A, Icilin evokes a dose- and time-dependent increase in glutamate within the dorsal striatum of rats. Amino Acids 30:3(307-9)2006 May
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