Scott Rawls, PhD

Research Interests

Dr. Rawls’ laboratory uses vertebrate (rats, mice) and invertebrate (planarians) models to investigate the pharmacology of drugs of abuse such as cocaine, amphetamines, opioids, and designer drugs.

Effects of glutamate transporter activators on rewarding, reinforcing, motivational, and drug-seeking effects of cocaine and opioids. Delineating the role of glutamate systems, especially glutamate transporters and receptors, in drug addiction is our major focus. 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. Our 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.

Characterization of the behavioral, neurochemical, cellular, and neurotoxic effects of designer cathinones contained in a street drug called ‘bath salts’. A more recent focus has been directed toward defining the neuropharmacological profile of a class of designer drugs called synthetic cathinones. These cathinones are found in dangerous street drug called ‘bath salts’ and possess abuse liability and toxicity. We have addressed an existing gap in the neuropharmacological profiles of synthetic cathionines, which is a lack of knowledge about their impacts on glutamate function, especially as it relates to whether reinforcing and drug-seeking properties of synthetic cathinones are mediated by the corticolimbic glutamate system and antagonized by glutamate-based therapies. Groundbreaking experimental studies on synthetic cathinones were directed toward the monoamine system; this approach was entirely logical because designer cathinones share structural characteristics with established psychostimulants that act as substrates or blockers at monoamine transporters. We are now providing the first comprehensive study into the role of the glutamate system in the neuropharmacological effects of synthetic cathinones. Our work will shed new information about how synthetic cathinones affect glutamate function in the nucleus accumbens of rats and how pharmacological approaches that modulate the cellular glutamate transport system affect direct reinforcing and drug-seeking effects of synthetic cathinones. The contribution is significant because it is the first step in a continuum of research that is expected to increase our understanding of how chronic exposure to synthetic cathinones influence amino acid neurotransmitter systems in brain reward circuits.

We have chosen to primarily investigate mephedrone (4-methylmethcathinone) (MEPH) and MDPV (methylenedioxypyrovalerone) based on their prevalence during the initial emergence of synthetic cathinones and different mechanisms of action. Synthetic cathinones have been classified according to two distinct mechanisms of action on the monoamine system: 1) substrate-type releasers such as MEPH that enter the presynaptic neuron and stimulate monoamine release and 2) blockers such as MDPV that act at monoamine transporters to block cellular reuptake of monoamines. Both of those mechanisms are represented by the compounds we have chosen to investigate. Further, MEPH and MDPV have provided templates for the design and synthesis of newer generation synthetic cathinone compounds, such as α-PVP, 4-MEC, naphyrone, and pentedrone, which only differ in structure from MEPH and MDPV by simple functional group substitutions. While there is no guarantee of mechanistic overlap, investigating glutamatergic mechanisms of MEPH and MDPV is expected to shed new mechanistic insight that may be relevant to the neuropharmacology of newly emerging cathinones and those that will emerge in the future.

Development of a hands-on, inquiry-based program/curriculum to teach the science of addiction and hazards of drug abuse to undergraduate, professional, and K-12 school students using a flatworm called planarians. My laboratory has demonstrated that planarians display mammalian-like responses to addictive substances. Some of our most important findings are that planarians display increased motility and stereotypy following acute exposure to addictive substances; abstinence-induced withdrawal behaviors following spontaneous discontinuation of exposure to addictive substances; sensitization of behavioral responses following repeated administration of addictive substances; a shift in environmental preference (dark to light) following conditioning with natural (sucrose) and drug rewards; and seizure-like activity following exposure to proconvulsanats that is prevented by clinical and preclinical anti-epileptic agents. Compared to mammals, advantages of planarians are the reduction of interpretive complications caused by mammalian pharmacokinetics (e.g. drug adsorption, distribution, metabolism, elimination, and blood-brain-barrier passage); ability to know drug concentration (as opposed to just dose), which is amenable to rigorous quantitative analysis; allowance for continuous drug exposure (an advantage over existing models that only allow for intermittent dosing or rely on mini-pumps to maintain constant drug concentrations); less susceptibility to higher-order confounders such as handling stress, testing-environment familiarity, procedural stresses, and anticipation of drug administration;  adaptability to studying broad classes of abused drugs, poly-drug exposure and different exposure patterns that mimic recreational and addictive drug use;  cost-effectiveness; a reproducible, sensitive, and quantifiable behavioral metric; ability to screen very small amounts of novel synthetic compounds that are of limited supply; and significant reduction in the use of mammals in research.

We are currently using the planarian model to develop and implement an inquiry-based educational program that will enable elementary, middle, high school, and undergraduate students to use living animals to study behavioral effects of commonly abused drugs (e.g. caffeine, alcohol, nicotine) and natural rewards (e.g. table sugar). My recently funded R25 NIDA grant is supporting these efforts related to the planarian model.

Educational Background

• NIDA Postdoctoral Fellowship, Lewis Katz School of Medicine at Temple University, 2000-2002
   
• PhD, East Carolina University School of Medicine, 1999
   
• BS, Chemistry, East Carolina University, 1990

Digital Bibliography

View PubMed Publications