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Biomedical subjects

Scott E Lukas

Publications and source records attributed to Scott E Lukas.

At least 19 recordsLinked to original sources

Negative cocaine effect expectancies are associated with subjective response to cocaine challenge in recreational cocaine users.

Although many studies have shown that cognitive effect expectancies are associated with drug use and drug treatment outcomes, few studies have compared effect expectancies with drug response following drug challenge. Healthy male and female volunteers (n=19, ages 21-35) who reported using cocaine 1-4 times per month completed the Cocaine Effect Expectancy Questionnaire (CEEQ: [Schafer, J. and Brown, S.A. (1991). Marijuana and cocaine effect expectancies and drug use patterns. Journal of Consulting and Clinical Psychology, 59, 558-565.]), were challenged with cocaine (0.9 mg/kg, i.n.), then completed a series of visual analog scales (VAS) and the Addiction Research Center Inventory (ARCI) at 15 min intervals for 3 h following cocaine administration. Significant positive correlations were found between global negative expectancies and peak responses on the VAS measures "Good," "Happy," "High," "Stimulated," and "Desire to Use Cocaine," and on the LSD subscale of the ARCI post-cocaine administration, and between global positive expectancies and the MBG subscale of the ARCI, and on VAS items "Anxious" and "Good" post-cocaine administration. Global positive expectancies also were positively correlated with peak systolic blood pressure, and global negative expectancies with peak heart rate after cocaine administration. These results suggest that negative and positive effect expectancies both play a complex role in the subjective experience of cocaine effects, and thus likely in the progression of non-use to recreational use, in the transition to abuse, and in individualized treatment strategies.

Adult↗

Incidence and patterns of polydrug use and craving for ecstasy in regular ecstasy users: an ecological momentary assessment study.

BACKGROUND: Previous studies employing retrospective assessments methods found that regular ecstasy users frequently use alcohol, marihuana and other drugs in combination with ecstasy. METHODS: Twenty-two participants (13 males, 9 females) wore a wrist actigraph/data recorder to record real-time drug use and ecstasy craving for 6 weeks. Rates of alcohol and drug use on ecstasy use versus non-use nights, and before, during, and after ecstasy use were analyzed with generalized estimation equations (GEE). Craving was modeled with GEE and linear mixed models. RESULTS: Approximately 70% of ecstasy uses occurred on Friday or Saturday nights. No drug was significantly more likely to be used on ecstasy use nights than comparison Friday and Saturday nights. On nights ecstasy was used, in general across all drugs assessed, use was more likely before and during than after ecstasy intoxication, while alcohol use was also more likely before than during ecstasy intoxication. Though low overall, craving for ecstasy increased over 24 h before use and was higher on Friday nights of weeks ecstasy was used on weekends than weeks it was not used. CONCLUSIONS: Use of ecstasy on a particular night may not be associated with any greater likelihood of using any other intoxicating drug, and use of other drugs on nights involving ecstasy use may simply reflect a "natural history" of drug-use nights that begins with alcohol, progresses to more intoxicating drugs, and ends with little drug use. Confirmation of these findings awaits further advances in the application of ecological momentary assessment methodologies.

Adult↗

Food intake and reward mechanisms in patients with schizophrenia: implications for metabolic disturbances and treatment with second-generation antipsychotic agents.

Obesity is highly prevalent among patients with schizophrenia and is associated with detrimental health consequences. Although excessive consumption of fast food and pharmacotherapy with such second-generation antipsychotic agents (SGAs) as clozapine and olanzapine has been implicated in the schizophrenia/obesity comorbidity, the pathophysiology of this link remains unclear. Here, we propose a mechanism based on brain reward function, a relevant etiologic factor in both schizophrenia and overeating. A comprehensive literature search on neurobiology of schizophrenia and of eating behavior was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) energy homeostasis, (2) food reward and hedonics, (3) reward function in schizophrenia, and (4) metabolic effects of the SGAs. A mesolimbic hyperdopaminergic state may render motivational/incentive reward system insensitive to low salience/palatability food. This, together with poor cognitive control from hypofunctional prefrontal cortex and enhanced hedonic impact of food, owing to exaggerated opioidergic drive (clinically manifested as pain insensitivity), may underlie unhealthy eating habits in patients with schizophrenia. Treatment with SGAs purportedly improves dopamine-mediated reward aspects, but at the cost of increased appetite and worsened or at least not improved opiodergic capacity. These effects can further deteriorate eating patterns. Pathophysiological and therapeutic implications of these insights need further validation via prospective clinical trials and neuroimaging studies.

Animals↗

Benztropine pretreatment does not affect responses to acute cocaine administration in human volunteers.

Benztropine (Cogentin ) was evaluated for its ability to block cocaine's physiological and subjective effects in humans. In healthy, recreational users of cocaine, placebo, or benztropine (1, 2, and 4 mg orally) was given 2 hr before subjects self-administered 0.9 mg/kg of cocaine intranasally. Measurements were made for 2 hr following cocaine administration, and plasma cocaine and cocaine metabolites were assayed. Cocaine produced typical increases in heart rate and alterations in self-reports measured by visual analog scales (VAS). Benztropine alone did not produce changes on any of these measures. Responses to cocaine with and without benztropine pretreatment were similar: benztropine did not change cocaine's effects. This study of one of the tropane-ring analogs that is approved for human use suggests this compound does not alter cocaine-induced effects, but just as importantly, does not produce any adverse behavioral or physiological effects. The exact therapeutic application of benztropine as a possible adjunct treatment for cocaine abuse in humans require further exploration.

Adult↗

Cerebellar vermis involvement in cocaine-related behaviors.

Although the cerebellum is increasingly being viewed as a brain area involved in cognition, it typically is excluded from circuitry considered to mediate stimulant-associated behaviors since it is low in dopamine. Yet, the primate cerebellar vermis (lobules II-III and VIII-IX) has been reported to contain axonal dopamine transporter immunoreactivity (DAT-IR). We hypothesized that DAT-IR-containing vermis areas would be activated in cocaine abusers by cocaine-related cues and, in healthy humans, would accumulate DAT-selective ligands. We used BOLD fMRI to determine whether cocaine-related cues activated DAT-IR-enriched vermis regions in cocaine abusers and positron emission tomography imaging of healthy humans to determine whether the DAT-selective ligand [11C]altropane accumulated in those vermis regions. Cocaine-related cues selectively induced BOLD activation in lobules II-III and VIII-IX in cocaine users, and, at early time points after ligand administration, we found appreciable [11C]altropane accumulation in lobules VIII-IX, possibly indicating DAT presence in this region. These data suggest that parts of cerebellar vermis mediate cocaine's persisting and acute effects. In light of prior findings illustrating vermis connections to midbrain dopamine cell body regions, established roles for the vermis as a locus of sensorimotor integration and motor planning, and findings of increased vermis activation in substance abusers during reward-related and other cognitive tasks, we propose that the vermis be considered one of the structures involved in cocaine- and other incentive-related behaviors.

Adult↗

A low-cost, MR-compatible olfactometer.

We present a design for an olfactometer, suitable for fMRI experiments, that can be constructed at extremely low cost. The olfactometer presents odors directly to the nose via a nasal cannula at unobtrusively low flow velocities, with no large assemblies required on or near the subject's face. The olfactometer can be controlled manually, or by computer via a serial interface. A validation study verified that the olfactometer reliably presents odors to test subjects. Errors and response latency times decreased with increased flow rate in an orderly manner, as expected.

Adult↗

Determination of puerarin in human plasma by high performance liquid chromatography.

Puerarin, an isoflavone C-glycoside, has been identified as the major active component isolated from Pueraria lobata (Kudzu) responsible for suppression of alcohol drinking. In order to conduct clinical studies of Kudzu's efficacy, a method for measuring its bioavailability and pharmacokinetic profile is needed. We have developed a gradient reversed-phase HPLC system for pharmacokinetic study of puerarin in human plasma. Solid-phase extraction was performed on an abselut Nexus cartridge (60 mg/3 ml) possessing adsorbent function with a recovery of >97% and 4-hydroxybenzoic acid was used as an internal standard. The HPLC assay was performed on a YMC ODS-A column (150 mm x 4.6mm i.d., 5 microm particle size). The HPLC mobile phase consisted of methanol/0.5% acetic acid with 20-35% methanol gradient at a flow-rate of 0.8 ml/min. The UV wavelength was set at 254 nm. Calibration of the overall analytical procedure gave a linear signal (r>0.999) over a puerarin concentration range of 5-500 ng/ml in human plasma. The lower limit of quantification was ca. at 8 ng/ml of puerarin in plasma. The detection limit (defined as signal-to-noise ratio of about 3) was approximately 3 ng/ml. The preliminary pharmacokinetic study after oral administration of the Kudzu capsules containing 400mg of puerarin to a healthy volunteer confirmed that the present method was suitable for determining puerarin in human plasma.

Chromatography, High Pressure Liquid↗

Probing reward function in post-traumatic stress disorder with beautiful facial images.

Reward dysfunction may be implicated in post-traumatic stress disorder (PTSD). This study applied a behavioral probe, known to activate brain reward regions, to subjects with PTSD. Male heterosexual Vietnam veterans with (n = 12) or without (n = 11) current PTSD were administered two tasks: (a) key pressing to change the viewing time of average or beautiful female or male facial images, and (b) rating the attractiveness of these images. There were no significant group differences in the attractiveness ratings. However, PTSD patients expended less effort to extend the viewing time of the beautiful female faces. These findings suggest a reward deficit in PTSD.

Beauty↗

Transdermal nicotine alters some of marihuana's effects in male and female volunteers.

Despite the fact that tobacco and marihuana are often used together, relatively little is known about the effects of this combination. In order to investigate the effects of the principal psychoactive component in tobacco smoke, nicotine, on marihuana-induced intoxication, we conducted a double blind, cross-over experiment using nicotine transdermal patches. Ten male and 10 female participants received either placebo or a 21 mg transdermal nicotine patch 4 h before smoking one of two marihuana cigarettes (1.99 or 3.51% delta-9-tetrahydrocannabinol (Delta(9) THC) content). Measurements of physiological activity (heart rate, blood pressure, and skin temperature) and subjective effects (self-reports of drug effects on visual analog scales (VAS) and the Addiction Research Center Inventory (ARCI)) were made periodically before and for 3h after smoking. Nicotine pre-treatment enhanced several responses to marihuana, in particular, heart rate, reports of "stimulated" on the visual analog scales, and scores on the Amphetamine scale of the ARCI. Male participants reported a more pronounced effect of marihuana that persisted longer than that of the female participants. Compared to the male participants, female participants experienced an attenuated response to marihuana and were less affected by the drug combination. The results of this study show that nicotine can have an important influence on the subjective and physiological effects of smoked marihuana. These effects have implications for the safety and efficacy of marihuana smokers who are self-medicating with the nicotine transdermal patch to manage their tobacco dependence.

Administration, Cutaneous↗

Effects of cortisol and cocaine on plasma prolactin and growth hormone levels in cocaine-dependent volunteers.

In rodents, corticosterone (cortisol in humans) facilitates cocaine self-administration purportedly via enhancement of dopaminergic activity in the brain. This study sought to assess central dopaminergic effects of cortisol in humans and to compare them to those of cocaine. Twelve cocaine-dependent individuals received an intravenous bolus of cortisol (0.5 and 0.2 mg/kg; n=6 for each dose) and cocaine (0.2 mg/kg) in a double-blind randomized placebo-controlled and counterbalanced fashion. Their plasma was assayed over the next 120 min for prolactin and growth hormone (GH), which are two neuroendocrine indices of dopaminergic function. Cortisol injections produced significant increases in GH, while cocaine resulted in significant decreases in prolactin. Placebo administration was associated with gradual declines in prolactin, but the levels at the 90- and 120-min time points were significantly lower after cocaine than after placebo infusion. These different neuroendocrine response profiles point to important differences between dopaminergic effects of cortisol and cocaine.

Adult↗

An extract of the Chinese herbal root kudzu reduces alcohol drinking by heavy drinkers in a naturalistic setting.

BACKGROUND: Of the available medications for treating alcohol-related problems, none are universally effective, and all have side effects that may limit their use. Extracts of kudzu containing a variety of isoflavones have been shown to reduce alcohol drinking in rats and hamsters. METHODS: The present study was designed to test the efficacy of a kudzu extract in a clinical population. Male and female "heavy" alcohol drinkers were treated with either placebo or a kudzu extract for 7 days and then given an opportunity to drink their preferred brand of beer while in a naturalistic laboratory setting. Participants served as their own controls, and order of treatment exposure was counterbalanced. Drinking behavior was monitored by a digital scale that was located in the top of an end table. RESULTS: Kudzu treatment resulted in significant reduction in the number of beers consumed that was paralleled by an increase in the number of sips and the time to consume each beer and a decrease in the volume of each sip. These changes occurred in the absence of a significant effect on the urge to drink alcohol. There were no reported side effects of kudzu treatment. CONCLUSION: These data suggest that an extract of this leguminous plant may be a useful adjunct in reducing alcohol intake in a naturalistic setting.

Adult↗

Oral methylphenidate challenge selectively decreases putaminal T2 in healthy subjects.

Despite the recent rise in oral methylphenidate (MPH) abuse, few studies have characterized the time course of oral MPH brain effects in human subjects. Accordingly, this study assessed the hemodynamic effects of oral MPH effects in 11 healthy young adults (six women), by measuring brain transverse relaxation times (T2). T2 can be interpreted as a surrogate marker for, and inversely correlated with, steady-state cerebral blood volume (CBV). Data were acquired from the caudate nucleus, putamen, and thalamus, using a 1.5 T MRI scanner at baseline and serially for 2 h following oral MPH administration (0.5 mg/kg). Physiological and subjective measures and plasma MPH levels also were examined. MPH induced a selective T2 decrease (-1.65+/-0.53 ms) in the putamen (F(6,54)=2.68, P<0.03). Heartrate, blood pressure and plasma MPH levels increased significantly after drug administration, as well as subjective ratings of "feeling drug effect". T2 decreases may reflect MPH-induced increases in putaminal blood volume. These data suggest that T2 relaxometry can be used to study the time course of regional cerebral blood volume responses to MPH and perhaps to other stimulant drugs.

Administration, Oral↗

Pretreatment with transdermal nicotine enhances some of ethanol's acute effects in men.

Nicotine and alcohol are often consumed together and smokers are more likely than non-smokers to drink alcohol. In spite of the high prevalence of the combined use of alcohol and nicotine, only a few laboratory studies have examined the effects of this drug combination in humans. The present study was conducted to further investigate the nature of nicotine/alcohol interactions by examining whether nicotine pretreatment via a transdermal patch (placebo or 21 mg) alters the subjective and physiologic effects of acute ethanol (0.4 and 0.7 g/kg) administration. Twelve male smokers who drank alcohol on an occasional basis provided informed consent to participate in the study. Subjective reports of feeling drunk, feeling ethanol's effects and ethanol-induced euphoria were increased by nicotine pretreatment. In addition, reports of desire to smoke a tobacco cigarette were significantly elevated after ethanol administration and were most pronounced during the active nicotine conditions. Heart rate was elevated by nicotine and ethanol-induced increases in heart rate were enhanced by nicotine pretreatment. The time to peak ethanol concentration was faster in the nicotine-patch condition and this paralleled the more rapid detection of ethanol effects after drinking the low-dose beverage. These findings suggest that nicotine enhances some of the positive subjective effects of acute ethanol and may help explain the high prevalence of the combined use of these two drugs.

Administration, Cutaneous↗

Effects of pharmacological doses of 2-deoxyglucose on plasma catecholamines and glucose levels in patients with schizophrenia.

RATIONALE: Several lines of evidence suggest that the pathophysiology of schizophrenia may be associated with altered noradrenergic and glucoregulatory function. OBJECTIVE: The aim of this study was to investigate these alterations during a perturbed homeostatic state. METHODS: Fifteen patients with schizophrenia and 13 healthy individuals were given a glucose deprivation challenge through administration of pharmacological doses of 2-deoxyglucose (2DG; 40 mg/kg), and their plasma was assayed over the next 60 min for concentrations of norepinephrine (NE), the intraneuronal NE metabolite dihydroxyphenylglycol (DHPG), epinephrine and glucose. RESULTS: 2DG induced significant increases in plasma NE, epinephrine and glucose levels in both groups with significantly greater NE and glucose increments in patients than in controls. For DHPG, 2DG produced increases in patients and decreases in the control subjects. NE responses correlated positively and significantly with the DHPG and glucose responses in schizophrenics, but not in controls. CONCLUSIONS: These findings suggest that patients with schizophrenia have exaggerated NE and glucose responses to an acute metabolic perturbation.

Adult↗

Reduced cortical gray matter density in human MDMA (Ecstasy) users: a voxel-based morphometry study.

The popular recreational drug, 3,4-methylenedioxymethamphetamine (MDMA) exerts its actions in part via blockade of serotonin and dopamine reuptake. Many animal and human studies have demonstrated long-lasting reductions in measures of central nervous system (CNS) serotonin function following MDMA administration. One emerging role of serotonin function in the CNS is a positive trophic effect via stimulation of intracellular signaling pathways and trophic factors. We hypothesized that human MDMA users might display neocortical gray matter reductions due to loss of serotonergically mediated trophic effects on cortical cells. However, unlike animal models, most human MDMA users worldwide are polydrug users, thereby complicating the assessment of MDMA toxicity in this group. Structural magnetic resonance imaging (MRI) scans of 31 MDMA polydrug users versus 29 non-MDMA users were compared using voxel-based morphometry (VBM) to assess regional brain gray and white matter concentration. VBM employs gray/white matter segmentation and statistical parametric mapping (SPM) analysis to calculate a voxel-wise comparison of regional gray or white matter concentration. Using this method, we consistently found several brain regions having decreased gray matter concentration in MDMA polydrug users. These regions were localized to neocortex in bilateral Brodmann area (BA) 18, left BA 21, and left BA 45, as well as bilateral cerebellum, and midline brainstem. Overall, these preliminary findings suggest that MDMA polydrug users have multiple regions of gray matter reduction, potentially accounting for previously reported neuropsychiatric impairments in MDMA users. Additional animal model and human studies of the CNS effects of MDMA and combined MDMA-polydrug toxicity are needed to further explain these findings. Potential explanations for our results including pre-existing brain differences predisposing to MDMA polydrug use, direct MDMA and polydrug toxicity, indirect changes due to MDMA and polydrug toxicity, or combinations of all these factors.

Adolescent↗

Phosphorous31 magnetic resonance spectroscopy after total sleep deprivation in healthy adult men.

STUDY OBJECTIVES: To investigate chemical changes in the brains of healthy adults after sleep deprivation and recovery sleep, using phosphorous magnetic resonance spectroscopy. DESIGN: Three consecutive nights (baseline, sleep deprivation, recovery) were spent in the laboratory. Objective sleep measures were assessed on the baseline and recovery nights using polysomnography. Phosphorous magnetic resonance spectroscopy scans took place beginning at 7 am to 8 am on the morning after each of the 3 nights. SETTING: Sleep laboratory in a private psychiatric teaching hospital. PARTICIPANTS: Eleven healthy young men. INTERVENTIONS: Following a baseline night of sleep, subjects underwent a night of total sleep deprivation, which involved supervision to ensure the absence of sleep but was not polysomnographically monitored. MEASUREMENTS AND RESULTS: No significant changes in any measure of brain chemistry were observed the morning after a night of total sleep deprivation. However, after the recovery night, significant increases in total and beta-nucleoside triphosphate and decreases in phospholipid catabolism, measured by an increase in the concentration of glycerylphosphorylcholine, were observed. Chemical changes paralleled some changes in objective sleep measures. CONCLUSIONS: Significant chemical changes in the brain were observed following recovery sleep after 1 night of total sleep deprivation. The specific process underlying these changes is unclear due to the large brain region sampled in this exploratory study, but changes may reflect sleep inertia or some aspect of the homeostatic sleep mechanism that underlies the depletion and restoration of sleep. Phosphorous magnetic resonance spectroscopy is a technique that may be of value in further exploration of such sleep-wake functions.

Adult↗

Psychosocial stress and the duration of cocaine use in non-treatment seeking individuals with cocaine dependence.

The aim of this study was to explore a potential link between psychosocial stress and cocaine dependence among 36 non-treatment-seeking individuals enrolled in a brain imaging protocol. Stress was assessed using computerized multidimensional instruments, including the Profile of Mood States (POMS) and Speilberger State-Trait Anxiety Inventory (STAI). Additional clinical assessments employed were the Addiction Severity Index and the Hamilton Rating Scale for Depression (HRSD). Based on the median POMS' tension-anxiety scale score the entire sample was divided into two groups, those with high and low levels of stress. The two groups (n = 16 and 20) were similar in terms of age, gender distribution, and severity of addiction. Compared with the low stress group, high-stress individuals displayed significantly longer duration of cocaine use, greater POMS, STAI-state, STAI-Trait, and HRSD scores. Our results replicate those of prior reports implicating stress in the course of cocaine dependence and extend these prior findings by 1) including a new subject population of non-treatment-seekers and 2) by suggesting that the stress-cocaine link may be generalizable to psychosocial stress and negative affective states defined by POMS, STAI, and HRSD scores.

Adult↗

Acute cortisol administration triggers craving in individuals with cocaine dependence.

Stress is often mentioned as a factor in the development of drug abuse. Twelve cocaine dependent individuals were administered a stress hormone, cortisol, along with cocaine and saline via intravenous boluses, in a double-blind, counterbalanced fashion. Self-reports of mood states were collected prior to, during, and 20 minutes after each bolus was administered. Cortisol produced significant increases in craving while cocaine significantly elevated all subjective ratings (ie, craving, high, rush, and low). These pilot data suggest that cortisol can induce a state that is associated with drug abuse.

Adult↗