NONHUMAN PRIMATE MODELS OF ADDICTION: BIOLOGICAL BASIS AND EXPERIMENTAL THERAPEUTICS
New England Regional Primate Research Center
Roger D. Spealman, Ph.D., James K. Rowlett, Ph.D.
Our research focuses on the use of novel nonhuman primate models of drug addiction in conjunction with other behavioral and neuropharmacological techniques to identify mechanisms of action underlying persistent drug use and to develop improved pharmacotherapies to combat dependence and relapse. Our earlier research established a functional link between the addictive effects of cocaine and its capacity to enhance dopamine neurotransmission in the central nervous system. Based on these findings we are currently investigating the therapeutic potential of novel dopamine transport inhibitors and dopamine receptor partial agonists as candidate maintenance medications and functional cocaine antagonists. Additional projects focus on the role of stress, drug cues and drug priming as triggers of relapse and on the biological basis for and treatment of combined cocaine-opiate ("speedball") addiction. Our research is designed to provide fundamental information on the neuropharmacological basis of cocaine and opiate dependence and to explore how pharmacological modulation of dopamine and other neurotransmitter systems can be exploited to develop improved treatments for addiction and relapse.
Key Words: Drug addiction, relapse, nonhuman primate models, mechanisms of action, medications development, stimulants, opiates.
Grant Support:
NIDA: DA00499, Control of Behavior by Abused Drugs
NIDA: DA11054, Nonhuman Primate Model of Cocaine Relapse and Treatment
NIDA: DA11541, Preclinical Development of Drugs for Stimulant Abuse (Subcontract)
NIDA: DA11928, Primate Model of Speedball Abuse: Mechanisms and Treatment
Project Sites: Division of Behavioral Biology, New England Regional Primate Research Center.
Project Director: R. D. Spealman, Ph.D., Professor of Psychobiology in the Department of Psychiatry, Associate Director for Scientific Affairs, and Chair, Division of Behavioral Biology, New England Regional Primate Research Center, One Pine Hill Drive, P.O. Box 9102, Southborough, MA 01772-9102.
Contact Person: Margaret Duggan, (508) 624-8034; FAX: (508) 624-8197
Training Opportunities: Three postdoctoral fellows currently receive training in these programs; additional positions are available. The New England Regional Primate Research Center maintains an active summer training program for prebaccalaureate students.
Representative Publications:
Platt, D. M., Rowlett, J. K., and Spealman, R. D., 2000. Dissociation of cocaine-antagonist properties and motoric effects of the D1 receptor partial agonists SKF 83959 and SKF 77434. Journal of Pharmacology and Experimental Therapeutics, 293:1017-1026.
Khroyan, T. V., Barrett-Larimore, R. L., Rowlett, J. K., and Spealman, R. D., 2000. Dopamine D1- and D2-like receptor mechanisms in relapse to cocaine-seeking behavior: Effects of selective antagonists and agonists. Journal of Pharmacology and Experimental Therapeutics, 294:680-687.
Rowlett, J. K., and Spealman, R. D., 1998. Opioid enhancement of the discriminative stimulus effects of cocaine: Evidence for involvement of m and d opioid receptors. Psychopharmacology, 140:217-224.
Spealman, R. D., 1996. Dopamine D3 receptor agonists partially reproduce the discriminative stimulus effects of cocaine in squirrel monkeys. Journal of Pharmacology and Experimental Therapeutics, 278:1128-1137.
Spealman, R. D., Bergman, J., and Rosenzweig-Lipson, S., 1997. Differential modulation of behavioral effects of cocaine by low- and high-efficacy D1 agonists. Psychopharmacology, 133:283-292.