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Seeking and Craving in Rats www.drugabuse.gov Volume 21, Number 4 U.S. Department of Health and Human Services | National Institutes of Health Neuropeptide Promotes Drug- ALSO IN THIS ISSUE Research Findings Seeking and Craving in Rats 7 Endorphin Derivative Inhibits Reward From Morphine and Nicotine Orexin emerges as a link in the chain of brain mechanisms in Rats regulating appetite for rewards. 8 Gene Experiment Confirms a Suspected discovered that people with narcolepsy lack orex- Cocaine Action BY LORI WHITTEN, NIDA Notes Staff Writer in-producing neurons. The finding suggested an 16 Study Links Anabolic explanation for a striking observation made in the Steroids to Brain Changes rexin, a neuropeptide that stimulates mid-1970s: People with narcolepsy rarely became in Adolescent Female eating and regulates wakefulness, also addicted to the potent stimulants used to treat the Mice fosters animals’ drug seeking and disorder at the time. Perhaps, some scientists spec- Director’s Perspective craving responses to drugs, according ulated, orexin contributes to the development of O 2 NIDA Will Contribute to to two NIDA-funded studies. The research teams, drug abuse. led by Drs. Glenda Harris and Gary Aston-Jones at Obesity Research OREXIN AND DRUG SEEKING the University of Pennsylvania and Drs. Stephanie Research in Brief Borgland and Antonello Bonci at the University of An observation in animals by Drs. Harris and 3 • Tracing NET California, San Francisco (UCSF), used different Aston-Jones also seemed to suggest a possible con- • Controlling ADHD experimental procedures and studied different nection. They noted that lateral hypothalamus (LH) Symptoms • Morphine drugs. Their findings, however, point to the same cells in the same area as orexin neurons were acti- Exposure in Rats conclusion: Augmenting orexin increases drug vated during drug seeking using a behavioral assay NIDA at Work seeking, while blocking it has the opposite effect. called conditioned place preference (CPP; for more Orexin, also called hypocretin, is produced by on CPP, see “Animal Experiments in Addiction Sci- 4 Division of Clinical neurons in the hypothalamus—a brain structure ence,” NIDA Notes Vol. 20, No. 5). After repeated Neuroscience and Behavioral Research that regulates hunger, thirst, sleep, and other morphine injections in one chamber of a test cage processes essential to survival. Scientists recently and saline in the other, rats gravitate to the drug- Reference Article paired area in an effort to re-expe- 11 Impacts of Drugs on rience the opiate effects. The time Neurotransmission OREXIN STIMULATION DRIVES DRUG-SEEKING Exposure to cues associated with drugs activate the orexin neurons (red), which stim- they spend in the area—their Bulletin Board ulates neruons in the brain’s mesolimbic reward pathway (blue). morphine place preference— 18 • Meeting Reviews indicates how intensely the drug 1 Drug Abuse and HIV Rewards (drugs or food) motivates drug seeking. When • Adolescent Inhalant Cues for Rewards 3 Drs. Harris and Aston-Jones Use Chemical Stimulation Mesolimbic Reward Pathway determined that the LH neurons Prefrontal Nucleus Ventral Tearoff Cortex Accumbens Tegmental Area activated during drug seeking pro- (PFC) (NAc) Shell (VTA) 2 duce orexin, they conducted fur- 19 Journal Highlights Drug Orexin neurons in lateral ther experiments. Abuse and HIV/AIDS hypothalamus (LH) The Pennsylvania researchers Adapted from Trends in Neurosciences 29(10):571-577, 2006. 20 What the Numbers Say first demonstrated that activa- [ Continued on page 6 ] NIDA Notes | Volume 21, Number 4 1 I DIRECTOR’S PERSPECTIVE By NORA D. VOLKOW, M.D., NIDA Director NIDA Notes EDITOR David Anderson Public Health Advisor, Office of Science Policy and Communications, National Institute on Drug Abuse MANAGING EDITOR Simon Weavers NIDA Will Contribute to MasiMax Resources, Inc. STAFF WRITERS Debra P. Davis Obesity Research Lori Whitten, Ph.D. MasiMax Resources, Inc. CONTRIBUTING WRITERS Carl Sherman The United States has a serious weight problem. Two-thirds of our adults are overweight Sarah Teagle, Dr. Ph. or obese. The prevalence of overweight among our children has nearly tripled since 1970. COPY EDITOR The consequences for the Nation’s health and economy are grave. Obesity has been Debra P. Davis MasiMax Resources, Inc. shown to decrease overall life expectancy and to increase the risk for cardiovascular dis- DESIGN/LAYOUT ease, type 2 diabetes, and other chronic conditions. Annually, it costs an estimated $117 bil- Maggie Bray lion or more in lost productivity and future earnings. To identify new strategies for preven- MasiMax Resources, Inc. tion and treatment, the National Institutes of Health (NIH) has established an Agency-wide EDITORIAL BOARD obesity task force and research plan (see obesityresearch.nih.gov). David Anderson, Chair; Public NIDA’s assignment on the 25-Institute task force represents a natural extension of the Health Advisor, Public Information and Liaison Branch, Office of Science Policy Institute’s research agenda. Addiction and compulsive eating both involve impaired impulse and Communications control and distorted valuation of the rewards to be derived from a certain behavior— Jessica Campbell Chambers, Ph.D., i.e., drug-taking or eating. The two conditions have roots in some of the same brain areas and Health Science Administrator, Division of Epidemiology, Services and Prevention circuits, including the hypothalamus, prefrontal cortex, and limbic system. The knowledge Research NIDA-funded scientists have developed of how those areas function normally and in the J.C. Comolli, Public Health Advisor, Division of Pharmacotherapies and Medical context of drug abuse undoubtedly will have great application to understanding the other Consequences of Drug Abuse compulsive behavior. Gaya Dowling, Ph.D., Deputy Branch In this issue, we report an exemplary illustration of the neurobiological overlap between Chief, Science Policy Branch, Office of Science Policy and Communications addiction and eating disorders: The hormone orexin appears to foster cravings for both food Lynda Erinoff, Ph.D., Associate Director, and drugs (see p. 1). Several other NIDA-supported studies are investigating compounds AIDS Research Program, Division of Epidemiology, Services and Prevention found to be effective in suppressing appetite and food intake. Some of the most promising Research produce their effects by blocking the brain’s cannabinoid receptors, which are targeted by Marsha F. Lopez, Ph.D. , Health Scientist THC, the active ingredient in marijuana (cannabis), a drug with marked effects on appetite. Administrator, Division of Epidemiology, Services and Prevention Research Researchers hope to translate this knowledge into medications for weight control, drug Gerald McLaughlin, Ph.D. , Chief, Grants abuse treatment, or both. Review Branch, Office of Extramural Affairs Mary Ellen Michel, Ph.D., Deputy EFFORTS BY OTHER INSTITUTES IN THE COLLABORATION INCLUDE: Director, Center for the Clinical Trials Network Ivan Montoya, M.D., M.P.H., Medical I A program, led by the National Institute of Diabetes and Digestive and Kidney Diseases Officer, Division of Pharmacotherapies and (NIDDK), to foster a multidisciplinary approach to clinical obesity research in areas such Medical Consequences of Drug Abuse Joni Rutter, Ph.D., Program Director, as metabolism, endocrinology, nutrition, cardiovascular biology, digestive diseases, Genetics and Molecular Neurobiology Research genetics, and behavioral sciences; and Branch, Division of Basic Neuroscience and Projects to combat pediatric obesity in primary care, day care, schools, and other commu- Behavioral Research I Vincent Smeriglio, Ph.D., nity settings by exploring effective methods to curb weight gain, including changes in Research Psychologist, Division of Clinical food and lifestyle choices. Neuroscience and Behavioral Research Frank Vocci, Ph.D., Director, We hope that further research into the many factors that contribute to obesity— Division of Pharmacotherapies and Medical including neural systems that modulate appetite and eating behavior—will lead to the devel- Consequences of Drug Abuse opment of new therapies for obesity as well as addiction. Cora Lee Wetherington, Ph.D., I Psychologist, Behavioral and Cognitive Science Research Branch, Division of Basic Neuroscience and Behavioral Research This publication was produced and printed by MasiMax Resources, Inc., under Contract No. N01DA-4-1117 from the National Institute on Drug Abuse. 2 NIDA Notes | Volume 21, Number 4 I RESEARCH IN BRIEF Highlights of recently published NIDA-supported studies disrupted in depression, atten- (besides alcohol and Holtzman and David White tion disorders, and stimulant marijuana) during the past first established that both peri- abuse. Researchers previously year. Of the 76 respondents adolescent (7 to 10 days before developed radiotracers for the who said they had been puberty onset) and adult male dopamine and serotonin trans- prescribed ADHD medications rats receiving 10 mg/kg/day of porters; the ability to image at some point during their morphine for 1 day or 3 consec- all three transporters in the lives, one-quarter said they had utive days exhibited similar brain will allow researchers to abused their medication to get increases in locomotor activity determine the role of each high, and 29 percent said they relative to age-matched rats neurochemical in the had given or sold it to someone receiving only saline. When the Tracing NET disorders. else. Dr. Himanshu Upadhyaya
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