NEUROIMAGING CENTER
Behavioral Psychopharmacology Research Laboratory | Research Developments and Highlights
The laboratory built a custom-designed end table that has a digital scale embedded (hidden) in the top tile insert in order to permit us to study drinking behavior in a natural setting. The room is decorated like a small studio apartment complete with refrigerator, reclining chair, TV/VCR, stereo, books, rugs, lamps, etc. Subjects are given the opportunity to take a beer from the refrigerator ad libitum. They are instructed to place the beer on the table, which then sends the weight to a computer located in an adjoining room. Each time the subject lifts the beer, the scale records the change in weight and stores the date and time of the event. This laboratory is being used in our assessment of kudzu and other herbal medicine's effects on drinking behavior.
Several innovative, one-of-a-kind devices have been built and perfected to study drug effects while subjects are undergoing magnetic resonance imaging (MRI) and spectroscopy (MRS) procedures. As a result, we can now study the real-time effects of smoked marihuana and tobacco on brain processes. Another unique device has been built to deliver odors to subjects while they are in the magnet. Through the presentation of a variety of both drug and non-drug odors, we can study the effects of cue-induced craving on brain mechanisms, anatomical locations, and behavioral responses.
The laboratory recently built a custom-designed standing platform that is being used to assess stance stability following a challenge with medications and during sleep deprivation studies. Unique computer interface programs were written for data collection and analysis.
Research Highlights
- Using the above-mentioned apparatus and laboratory set-up, demonstrated that a week's treatment of extract of the herbal medication Kudzu significantly reduced alcohol consumption in heavy drinkers. A second 4-week outpatient study similarly demonstrated that Kudzu significantly reduced alcohol intake in alcohol-abusing and alcohol-dependent individuals.
- Demonstrated the bioavailability and pharmacokinetic properties of kudzu following single and repeated administrations.
- Demonstrated that a new form of acupuncture using electrical stimulation at specific acupuncture points reduces drug intake during an outpatient trial and may affect cue-induced drug craving in a laboratory setting.
- Demonstrated through the use of neurophysiologic polysomnographic (PSG) measurements and [31]P MRS Neuroimaging that methadone-maintained persons have marked differences compared to control subjects in recovery sleep following sleep deprivation which is accompanied by alterations in brain high-energy phosphates.
- Discovered that pretreatment with a nicotine transdermal patch attenuates cocaine-induced increases in reports of "high" and "stimulated" and increases the latency to detect cocaine effects and cocaine-induced euphoria. These nicotine-induced changes in cocaine effects were observed in the absence of any changes in heart rate, skin temperature, blood pressure or plasma cocaine, benzoylecgonine or ecgonine methylester concentrations.
- Studied several potential pretreatment compounds for their ability to block cocaine's physiological and behavioral effects. Compounds that block cholinergic, dopaminergic or serotonergic receptors have generally lacked ameliorative effects.
- Discovered that pretreatment with ethanol increases the absorption of Δ9-tetrahydrocannabinol (THC) from smoked marihuana and consequently explains why this drug combination is so popular. The enhanced subjective effects after the combination paralleled the increased plasma levels.
- Demonstrated that short-term treatment with citicoline does not result in any change in cocaine-induced toxicity when individuals are challenged with moderate doses. This study is a prelude to a more extensive treatment trial of citicoline in chronic cocaine-dependent individuals.
- Documented the craving for ecstasy 24 hours prior to and 24 hours after use and the pattern of other drugs used in conjunction with ecstasy.
- Demonstrated that bupropion (Zyban®) can alleviate some of the symptoms experienced during withdrawal from chronic, heavy marihuana use.
- Recently demonstrated that there are individual differences in decision-making that are correlated with drug use history. Interestingly, these differences were correlated with smoking history as well as experience with illicit drugs. The procedure required that the subjects choose between two "ideal" solutions. One was ideal, from the perspective that the experiment consisted of but one trial. The other was ideal from the perspective that the experiment consisted of a series of trials (the actual situation). Methadone clinic patients generally failed to learn the multi-trial solution, whereas non-methadone clinic patients shifted to the multi-trial solution over the course of the experimental session. Among the non-methadone clinic subjects, individuals who had quit smoking were most likely to prefer the multi-trial solutions, whereas current smokers were indistinguishable from the methadone subjects. The results show a correlation between quitting drug use and decision making (e.g., the differences between current and ex-smokers). To our knowledge this is the strongest demonstration to date of (1) cross-situational individual differences in decision making and (2) a robust correlation between performance in a simple behavioral procedure and long-term drug use.
- In a new version of the experiment described above, introduced a tutorial that points out that the computer choice procedure has two solutions, depending on the time horizon (either one-trial or a series of consecutive trials). Individuals differ in whether the tutorial experience influences performance in subsequent choice games. We are currently testing whether the ability to benefit from the tutorial is correlated with drug use history. Depending on the results, we will test whether performance in our choice procedure predicts relapse and abstinence in smoking cessation programs.