Behavioral Neuroscience Research Branch
Preclinical Pharmacology Section
Mission Statement
The Preclinical Pharmacology Section conducts research in animals on the environmental, historical, and pharmacological determinants of the behavioral and cardiovascular effects of psychoactive drugs, with an emphasis in recent years on psychomotor stimulants, particularly nicotine, cocaine and methamphetamine. Research focuses on the effects of drugs on ongoing, learned behavior sustained by food reward or electric-shock avoidance, on the reinforcing (rewarding) and discriminative-stimulus effects of drugs, and on the cardiovascular and neuropharmacological consequences of acute or chronic drug exposure. Neuropharmacological mechanisms underlying behavioral responses we measure are facilitated by collaborative projects both within and outside the IRP and by an in-vivo microdialysis facility. The goal is to utilize in-vivo animal paradigms to elucidate behavioral and neuropharmacological mechanisms that underlie the actions of abused psychoactive drugs and to utilize this knowledge to develop potential treatment approaches for compulsive licit (nicotine) or illicit drug use and abuse.
Program Areas
Current research efforts of the Preclinical Pharmacology Section are focused in the three program areas. The first "Behavioral, neuropharmacological and molecular studies of the reinforcing (rewarding) and discriminative-stimulus properties of delta-9-tetrahydrocannabinol (THC) and other cannabinoids" is based on our recent studies showing for the first time that THC is able to persistently maintain high rates of i.v. self-administration behavior in monkeys. The second program area "Serotonergic, histaminergic and adenosinergic involvement in the behavioral effects of methamphetamine and amphetamine: Neurochemical and molecular mechanisms" grew out of our involvement over the past seven years with research on the MAO-B inhibitor seligiline (L-deprenyl) and its analogs, which are metabolized to the methamphetamine- and amphetamine-like compounds. The third program area "Alteration of the behavioral effects of nicotine, amphetamine, methamphetamine and cocaine after chronic exposureto caffeine or selective adenosine antogonists or agonists: Neurochemical and molecular mechanisms" grew out of our longstanding interest in behavioral actions of nicotine, which started with our findings that i.v. nicotine can serve as a reinforcer in experimental animals, providing the first clear animal model of nicotine dependence. A fourth program area, "Role of incentive-motivation and discriminative stimulus effects in drug-seeking and drug-taking," grew out of our long-term interests in the elucidating the behavioral principles controlling drug self-administration. A fifth area, "Cardiovascular effects of abuse drugs," is directed at determining the pharmacological mechanisms for these effects as well as determining how abused drugs might interact with treatment agents. The goal is to insure the safety of any treatment used in humans. The sixth program "Interactions between adenosine, dopamine and glutamate receptors in the striatum" deals with the analysis at behavioral (motor activity, drug discrimination), neurochemical (C-Fos immunohistochemistry) and molecular (protein-protein interaction) levels of multiple interactions between subtypes of adenosine, dopamine and glutamate receptors. Evidence has already been found for the existence of heteromeric complexes between some of these receptors (A1R-D1R, A2AR-D2R, A2AR-mGlu5R), which can have implications for the treatment of basal ganglia disorders and drug abuse.
Name: Steven R. Goldberg
Title: Section Chief
Telephone Number: (410) 550-1522
Name: Charles W. Schindler, Ph.D.
Title: Senior Investigator
Telephone Number: (410) 550-1454
Synopsis of Research
Steven Goldberg - Research is conducted with experimental animals on the behavioral actions of drugs of abuse, both in producing reinforcing, punishing and discriminative-stimulus effects and in altering behavior controlled by non-drug events such as food or electric shock. An overall goal of the research is to understand how drugs affect whole animals, with an eventual goal being the development of effective clinical treatment regimens. Studies cover a wide range of topics including the pharmacology of illicit psychomotor stimulants such as methamphetamine and cocaine, licit stimulants such as nicotine and caffeine, opioids and marijuana. Many studies focus on alterations in the acquisition, maintenance and reduction of drug-seeking behavior or and neurochemical and molecular mechanisms underlying these behavioral actions.Research is carried out in squirrel monkeys and rats using a variety of in vivo behavioral and neuropharmacological procedures, including (1) assessing motivational effects of drugs and their neural substrates using intravenous drug self-administration procedures, (2) quantifying behavioral effects of drugs using shedules of either food delivery or electric shock postponement as baselines, (3) determining subjective effects of drugs as discriminative stimuli using two-lever choice procedures and (4) quantifying changes in neurotransmitter levels in discrete areas of the brain produced by drugs using microdialysis techniques.
Dr. Schindler - The major objective of the Psychophysiology Unit of the Preclinical Pharmacology Section is to investigate the behavioral and physiological effects of drugs of abuse, with a particular emphasis on the psychomotor stimulants. These studies are directed both at determining the mechanisms of action involved in these effects, and in assisting in the development of pharmacotherapies for stimulant addiction. A number of techniques are used to study behavior, including drug self-administration, schedule-controlled behavior, classical conditioning, locomotor activity and place preference. In the study of the physiological effect of drugs of abuse, we have focused on cardiovascular effects. For these studies, blood pressure, heart rate and ECG are monitored following drug administration.
|
|
|
Behavioral Neuroscience Research Branch
|
|
