EFFECTS OF CHRONIC DRUG COMBINATION TREATMENTS ON THE REINFORCING AND COGNITIVE EFFECTS OF COCAINE IN RODENTS AND MONKEYS Michael A. Nader, PI Paul W. Czoty, Thomas J. Martin, Mark J. Ferris, Mei-Chuan Ko, Daniel Yohannes, Co-Is The goal of this Project is to achieve a better understanding of the pharmacological determinants of the reinforcing effects of cocaine in rodent and nonhuman primate models of drug abuse. In the previous funding period, we found that monoamine releasers d-amphetamine, phenmetrazine (PM) and phendimetrazine (PDM) effectively decreased cocaine self-administration in rats and monkeys. For the studies proposed in Project 1, we will incorporate a strategy that involves drug combinations in order to meet two goals: (1) reduce the amount of drug (i.e., PM or PDM) necessary to decrease cocaine self-administration and (2) improve treatment efficacy. For all studies, one of the drugs (Drug A) will be PM (in rats) and PDM (in monkeys). The combination drug (Drug B) will be based on input from our clinicial colloborators and be a compound that improves cognitive performance in animals with a cocaine history.
In Specific Aim 1, rats will self-administer cocaine under a long-access 6-hr session; some rats will then be tested in two paradigms designed to assess cognition/attention/impulsivity, the delayed discounting procedure and the 5-choice serial reaction time task. Drug B candidates that show remediation of cocaine-induced disruptions in cognitive performance will be tested in another group of rats self-administering cocaine and co-treated with PM. Drug B candidates that effectively reduce rodent self-administration will be tested in nonhuman primates (Specific Aim 2) under two different cocaine access conditions - progressive-ratio and concurrent food-cocaine choice. If the combination of PDM and Drug B effectively decreases cocaine self-administration under either condition, the effects of the combination on cognitive performance and physiology, as assessed with telemetry, will be examined in these same monkeys (Specific Aim 3). These studies combine chronic drug treatment and drug combinations under multiple behavioral conditions in rats and monkeys and should provide valuable translational information for the development of novel cocaine pharmacotherapies.

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National Institute on Drug Abuse (NIDA)
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Wake Forest University Health Sciences
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Melchior, James R; Jones, Sara R (2017) Chronic ethanol exposure increases inhibition of optically targeted phasic dopamine release in the nucleus accumbens core and medial shell ex vivo. Mol Cell Neurosci 85:93-104
Blume, Lawrence C; Patten, Theresa; Eldeeb, Khalil et al. (2017) Cannabinoid Receptor Interacting Protein 1a Competition with ?-Arrestin for CB1 Receptor Binding Sites. Mol Pharmacol 91:75-86
John, William S; Martin, Thomas J; Nader, Michael A (2017) Behavioral Determinants of Cannabinoid Self-Administration in Old World Monkeys. Neuropsychopharmacology 42:1522-1530
Brodnik, Zachary D; Ferris, Mark J; Jones, Sara R et al. (2017) Reinforcing Doses of Intravenous Cocaine Produce Only Modest Dopamine Uptake Inhibition. ACS Chem Neurosci 8:281-289
Howlett, Allyn C; Abood, Mary E (2017) CB1 and CB2 Receptor Pharmacology. Adv Pharmacol 80:169-206
Gould, Robert W; Czoty, Paul W; Porrino, Linda J et al. (2017) Social Status in Monkeys: Effects of Social Confrontation on Brain Function and Cocaine Self-Administration. Neuropsychopharmacology 42:1093-1102
Namjoshi, Sanjeev V; Raab-Graham, Kimberly F (2017) Screening the Molecular Framework Underlying Local Dendritic mRNA Translation. Front Mol Neurosci 10:45
Wesley, Michael J; Lile, Joshua A; Fillmore, Mark T et al. (2017) Neurophysiological capacity in a working memory task differentiates dependent from nondependent heavy drinkers and controls. Drug Alcohol Depend 175:24-35
Siciliano, Cody A; Saha, Kaustuv; Calipari, Erin S et al. (2017) Amphetamine reverses escalated cocaine intake via restoration of dopamine transporter conformation. J Neurosci :
Luessen, D J; Sun, H; McGinnis, M M et al. (2017) Chronic intermittent ethanol exposure selectively alters the expression of G? subunit isoforms and RGS subtypes in rat prefrontal cortex. Brain Res 1672:106-112

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