Addiction research
This research is directed at motivational processes underlying drug addiction and alcoholism. At present there is no clear explanation of compulsive and abnormal intake of psychotopic substances and the costs of addictive behaviors to the society continue to rise. Studies are designed to investigate the biopsychological mechanisms of changes in behavior produced by abused drugs. Our working hypothesis is that these substances interact with normal motivational functions such as eating, drinking or pain avoidance and this is reflected in learning and conditioning produced by substances of abuse. The basic experimental paradigms measure behaviors and their physiological correlates that are expected to give information on increased risk for consumption of an addictive substance. A further goal is to investigate the involvement in motivational processes of drug tolerance and physical dependence.
The program is primarily centered around a new interdisciplinary research initiative in the addiction field at the University of Tübingen funded by the federal and regional governments. However, the program extends existing interests at the insitute in emotion, learning and adaption. The institute is also involved in legal assessments of individuals who have problems with alcohol and driving and considerable research has been carried out on smoking and smokers with regard to the effect of nicotine intake on pain and cardiovascular function.
The work is comparative in nature and the program at the institute is still in the initiation phase. Thus, it involves the examination of drug-related motivational effects in animals using test systems analogous to those applied in normal humans and in selected populations of addicted individuals. Whereas the existing animal research stemmed from cooperations with other institutions (Addiction Research Foundation of Ontario and the Department of Pharmacology, University of Toronto, Toronto, Canada; Profs. H. Kalant und Y. Israel). Similarly, work on drug-related effects in natural settings in humans is part of an ongoing collaboration with the Institute of Psychology at the University of Cologne (Prof. E. Stephan). Facilities to examine addictive processes in non-laboratory settings is also expected to be in operation in the institute in the first half of 1995. These facilities will be used to identify and analyse the extent to which drug related cues in the normal environment of an addicted individual are involved in the development and maintenance of drug produced conditioned responses and craving for more drug.
The expected information from this research is relevant for better prevention of drug abuse and more effective therapy.
Relation between the motivational effects and the physical signs of drug withdrawal in animal models
Whereas it is widely believed that many addicts continue to use drugs because of the fear of the physiological changes produced by drug withdrawal (abstinence syndrome), there are few clear data on the withdrawal reaction as a motivator of continued drug intake. Simple procedures (preference conditioning) were recently developed to test directly for motivational effects of drug withdrawal in animals. Thus, it was demonstrated that the magnitude of commonly expressed somatic signs of opiate withdrawal do not correlate with the magnitude of the aversive effects of opiate withdrawal. For example, a study was carried out to measure directly the motivational effects of withdrawal from two abused substances that are not opiates: amphetamine and nicotine. Rats were treated with drugs using a slowly released, subcutaneously implanted drug depot, a standard method in the literature for studying physical dependence on these substances. Withdrawal was induced using appropriate pharmacological antagonists and the motivational test was the taste conditioning test. Whereas amphetamine withdrawal was found to be motivationally neutral (produced neither conditioned aversion nor preference), withdrawal from nicotine produced a conditioned preference; this was interpreted to mean that nicotine withdrawal was positively motivating. Also seen was a lack of a close parallel between the physical signs and the motivating effect of withdrawal for the quasi-withdrawal model of withdrawal phenomena. It was concluded that an aversive effect is not an obligatory consequence of withdrawal from a substance that is abused by humans. Moreover, the findings indicate the need to reexamine the traditional concept that the withdrawal from different classes of abused substances produce similar withdrawal-associated aversive effects.
Mucha, R. F., Pauli, P., Perl, F., Flor, H., Fassos, F. F., Walker, M., J., K., Birbaumer, N. (1995) Entzugsinduzierte motivationelle Eigenschaften und körperliche Symptome korrelieren nicht in Tiermodellen der Opiat-, Amphetamin- oder Nikotinabhängigkeit. Sucht , (im Druck).
Mucha, R. F., Fassos, F., F., Perl, F., M., (1995) Withdrawal-like effects of pentylenetetrazol and valproate in the naive organism: a model of motivation produced by opiate withdrawal? Drug and Alcohol Dependance, in press .
Monitoring of addictive behavior in humans in natural settings
Animal studies indicate that environmental cues (rooms, lights, sounds) paired with a drug effect serve as conditioned stimuli and come to modify the normal effects of drugs. Various aspects of the natural environment of an addict serve as signals for drug intake. To eventually test how drug effects in an addicted individual are modulated in an actual drug-taking situation, we have been developing and testing methods using smokers as a test model. To illustrate the value of this methodogy a study was carried out to examine a self-report made by many smokers that smoking during their daily activities has a relaxing effect; this observation contrasts with findings from many laboratory studies that smoking is physiologically activating.
The test system was a portable computer with sensors for collecting psychophysiological and behavioral data. Light to moderate cigarette smokers were investigated and changes in heart rate provided data on the physiological effect of smoking. While going about their daily routines subjects were required to carry the computer and smoke their cigarettes with a puff recorder. The data indicated that during smoking there was indeed a decrease in heart rate as compared to that measured just before. Data from an activity sensor indicated that this effect was not due to changes in general body movement. However, from a sensor for the sitting position it was found that subjects often sat down to smoke a cigarette, thereby confounding the overall changes in heart rate. Examination of smoking effects on heart rate only in the sitting position confirmed the typical laboratory observation that smoking increased baseline heart rate. The findings indicate the value of objective measurements to collect interpretable and accurate data on addictive behavior in natural settings. They further confirm the need for information on drug effects in the actual drug taking situation to fully understand addictive behavior in humans.
Mucha, R. F., Weiss, R. V., Mutz, R., Stephan, E. (1993). Examination of motivated behavior and its correlates in humans in natural settings: Society of Neuroscience Abstracts 16, 1458.
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Hubert Preißl
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