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UT Health San Antonio
Department of Cell Systems and Anatomy
The abuse of prescription opioids is a growing public health problem. Prescription opioid abuse often starts in adolescence, but most of what we know about opioids is from research in adults. Our lab examines abuse-related effects of morphine in adolescent mice and the mechanisms underlying adolescent vulnerability to opioid abuse.
Results show that adolescents are more sensitive than adults to the acute stimulant effects of morphine, but less sensitive to its sedative effects. Thus, adolescents show abuse-enhancing and abuse-limiting effects of morphine that differ from those in adults. Using animal models to examine the mechanisms underlying this heightened vulnerability yields knowledge that can help to more effectively prevent and treat adolescent prescription opioid abuse.
Funding Agency ASPET Title ASPET Fellowship Program for Undergraduate Students Status Active Period 6/2007 - Present Role Contributor Grant Detail Funding Agency NIMH Title Organic Cation Transporter 3: A New Target for Antidepressant Drug Development Status Active Period 3/2012 - 11/2016 Role Co-Principal Investigator Grant Detail The goal of these studies is to develop selective pharmacological tools with which to validate organic cation transporter 3 as a target for novel antidepressant medications. Funding Agency NIH Title Delay Discounting: Effects of Drug Dependence and Withdrawal Status Active Period 7/2010 - 6/2016 Role Co-Investigator Grant Detail Funding Agency NIH/NIDA Title Discriminative Stimulus Effects of Opioid Withdrawal Status Active Period 2/2010 - 1/2016 Role Co-Investigator Grant Detail Investigate opioid dependence and withdrawal in monkeys and pigeons using drug dependence procedures in order to identify and characterize novel pharmacotherapeutic approaches for the treatment of opioid abuse.
Daws L, Mitchell N, Horton R, Vitela M, Gould G, Koek W. Transient increases in expression and function of the plasma membrane monoamine transporter may contribute to treatment resistant depression during juvenile and adolescent periods; 2014 Dec. (ACNP meeting). Mitchell NC, Horton RE, Vitela M, Gould GG, Koek W, Daws LC. Antidepressant potential of organic cation transporter blockade: the role of norepinephrine; 2014 Apr. (ASPET meeting). Koek W. Morphine-induced Conditioned Place Preference and effects of Morphine Pre-exposure in Adolescent and Adult Mice; 2013 Dec. (ACNP meeting). Koek W. Long-lasting sensitization induced by a single exposure to morphine: age-related differences in mice; 2013 Jun. (CPDD meeting). Koek W. A single exposure to morphine induces long-lasting sensitization: age-related differences in mice; 2013 Apr. (ASPET meeting).
Krause-Heuer AM, Fraser-Spears R, Dobrowolski JC, Ashford ME, Wyatt NA, Roberts MP, Gould GG, Cheah WC, Ng CKL, Bhadbhade M, Zhang B, Greguric I, Wheate NJ, Kumar N, Koek W, Callaghan PD, Daws LC, Fraser BH. Evaluation of the antidepressant therapeutic potential of isocyanine and pseudoisocyanine analogues of the organic cation decynium-22 Eur J Med Chem 2017 Sep;137:476-487. Mitchell NC, Bowman MA, Gould GG, Koek W, Daws LC. Ontogeny of Norepinephrine Transporter Expression and Antidepressant-Like Response to Desipramine in Wild-Type serotonin Transporter Mutant Mice Journal of Pharmacology and Experimental Therapeutics 2017 Jan;360(1):84-94. Mecklenburg J, Patil M, Koek W, Akopian AN. Effects of local and spinal administrations of mu-opioids on postoperative pain in aged versus adult mice Pain Rep 2017 Jan;2(1). Moerke MJ, De Moura FB, Koek W, McMahon LR. Effects of nicotine in combination with drugs described as positive allosteric nicotinic acetylcholine receptor modulators in vitro: discriminative stimulus and hypothermic effects in mice Eur J Pharmacol 2016 Sep;786:169-178. Mitchell NC, Gould GG, Koek W, Daws LC. Ontogeny of SERT Expression and Antidepressant-like Response to Escitalopram in Wild-Type and SERT Mutant Mice J Pharmacol Exp Ther 2016 Aug;358(2):271-281. Koek W. Morphine-induced conditioned place preference and effects of morphine pre-exposure in adolescent and adult male C57BL/6J mice Psychopharmacology (in press) 2016 Jul;233(11):2015-2024. Serafine KM, Bentley TA, Kilborn DJ, Koek W, France CP. Drinking sucrose or saccharin enhances sensitivity of rats to quinpirole-induced yawning European Journal of Pharmacology 2015 Oct;764:529-536. Gerak LR, Zanettini C, Koek W, France CP. Cross-tolerance to cannabinoids in morphine-tolerant rhesus monkeys Psychopharmacology (Berl) 2015 Oct;232(19):3637-3647. Iderberg H, McCreary AC, Varney MA, Kleven MS, Koek W, Bardin L, Depoortere R, Cenci MA, Newman-Tancredi A. NLX-112, a novel 5-HT1A receptor agonist for the treatment of L-DOPA-induced dyskinesia: Behavioral and neurochemical profile in rat Exp Neurol 2015 Sep;271:335-350. Collins GT, Chen Y, Tschumi C, Rush EL, Mensah A, Koek W, France CP. Effects of consuming a diet high in fat and/or sugar on the locomotor effects of acute and repeated cocaine in male and female C57Bl/6J mice Experimental and Clinical Psychopharmacology 2015 Aug;23:228-237. Koek W, Gerak LR, France CP. Effects of amphetamine, morphine, and CP55, 940 on Go/No-Go task performance in rhesus monkeys Behav Pharmacol 2015 Aug;26(5):481-484. Paredes RM, Piccart E, Navaira E, Cruz D, Javors MA, Koek W, Beckstead MJ, Walss-Bass C. Physiological and behavioral effects of amphetamine in BACE1 (-/-) mice Genes Brain Behav 2015 Jun;14(5):411-418. Serafine KM, Bentley TA, Koek W, France CP. Eating high fat chow, but not drinking sucrose or saccharin, enhances the development of sensitization to the locomotor effects of cocaine in adolescent female rats Behav Pharmacol 2015 Apr;26(3):321-325. Mitchell, N.C., Koek, W. and Daws, L.C. Antidepressant-like effects and basal immobility depend on age and serotonin transporter genotype Genes, Brain and Behavior 2015 Mar;4(17):543-549. Koek W. Effects of repeated exposure to morphine in adolescent and adult male C57BL/6J mice: age-dependent differences in locomotor stimulation, sensitization, and body weight loss Psychopharmacology (Berl) 2014 Apr;231(8):1517-1529. Collins GT, Jackson JA, Koek W, FRance CP. Effects of dopamine D(2)-like receptor agonists in mice trained to discriminate cocaine from saline: influence of feeding condition Eur J Pharmacol 2014 Apr;729:123-131. Mitchell NC, Gould GG, Smolik CM, Koek W, Daws LC. Antidepressant-like drug effects in juvenile and adolescent mice in the tail suspension test: Relationship with hippocampal serotonin and norepinephrine transporter expression and function Front Pharmacol 2013 Oct;4:131-131. Horton RE, Apple DM, Owens WA, Baganz NL, Cano S, Mitchell NC, Vitela M, Gould GG, Koek W, Daws LC. Decynium-22 enhances SSRI-induced antidepressant-like effects in mice: uncovering novel targets to treat depression J Neurosci 2013 Jun;33(25):10534-10543. Koek W, Cheng K, Rice KC. Discriminative stimulus effects of the GABAB receptor-positive modulator rac-BHFF: comparison with GABAB receptor agonists and drugs of abuse J Pharmacol Exp Ther 2013 Mar;344(3):553-560. Daws LC, Koek W, Mitchell NC. Revisiting serotonin reuptake inhibitors and the therapeutic potential of "uptake-2" in psychiatric disorders ACS Chem Neurosci 2013 Jan;4(1):16-21. Maguire DR, Li JX, Koek W, France CP. Effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) and quipazine on heroin self-administration in rhesus monkeys Psychopharmacology (Berl) 2013 Jan;225(1):173-185.
Hensler JG, Artigas F, Bortolozzi A, Daws LC, De Deurwaerdere P, Milan L, Navailles S, Koek W. Catecholamine/serotonin interactions: systems thinking for brain function and disease Adv Pharmacol 2013 Jan;68:167-197.