Biomedical subjects

S E Lukas

Publications and source records attributed to S E Lukas.

At least 37 records · Page 2Linked to original sources

PubMed1998

Cocaine administration induces human splenic constriction and altered hematologic parameters.

Cocaine is a potent vasoconstrictor that has been shown to alter hemoglobin, hematocrit, and red blood cell counts in both animals and humans. The present study evaluated whether cocaine administration induces splenic constriction in men and whether spleen-volume changes temporally correlate with altered hematologic parameters. Spleen volume was assessed at baseline and after cocaine administration (0.4 mg/kg) by using magnetic resonance imaging. A group of five healthy men, aged 31 +/- 2 (SE) yr and reporting occasional cocaine use (13 +/- 5 lifetime exposures), participated. Cocaine reduced spleen volume by 20 +/- 4% (P < 0.03) 10 min after drug administration. Spleen volume returned to normal (101 +/- 3% baseline) within 35 min after cocaine administration, indicating that the reduction is a transient phenomenon. In subjects administered cocaine from whom blood samples were obtained (n = 3), cocaine increased hemoglobin levels, hematocrit, and red blood cell count to 104.5 +/- 0.9, 105.6 +/- 1.2, and 106.5 +/- 1.0% of baseline levels, respectively (P < 0.03), but it did not alter white blood cell and platelet counts. Placebo administration (n = 5) did not alter hematologic parameters. These results suggest that cocaine induces splenic constriction in humans, and this may contribute to temporally concordant hematologic parameter changes. These events may help to preserve or increase tissue oxygenation in periods of high oxygen demand and/or increased vascular resistance.

Adult↗

PubMed1998

Functional magnetic resonance imaging of human brain activation during cue-induced cocaine craving.

OBJECTIVE: Functional magnetic resonance imaging (MRI) was used to test whether brain activation was detectable in regions previously associated with cocaine cue-induced craving. METHOD: Blood oxygenation level dependent (BOLD) functional activation was measured during presentation of audiovisual stimuli containing alternating intervals of drug-related and neutral scenes to six male subjects with a history of crack cocaine use and six male comparison subjects. RESULTS: Significant activation was detected in the anterior cingulate and left dorsolateral prefrontal cortex in the cocaine-using group. In addition, a correlation between self-reported levels of craving and activation in these regions was found. CONCLUSIONS: These results suggest that functional MRI may be a useful tool to study the neurobiological basis of cue-induced craving.

Adult↗

PubMed1996

P300 assessment of opiate and cocaine users: effects of detoxification and buprenorphine treatment.

We assessed cognitive function following heroin and cocaine detoxification and investigated whether buprenorphine treatment improves the disruptive effects of detoxification. Three groups of male volunteers meeting DSM-III-R criteria for concurrent opiate and cocaine dependence were tested using an auditory oddball paradigm before and after detoxification, and again on the 15th day of either buprenorphine or placebo treatment. There were no significant differences in P300 amplitude, latency, or topographic distribution between drug-dependent subjects and controls on admission day. Following detoxification there was a significant decrease in P300 amplitude in the drug-dependent group at a time when self-reported signs of withdrawal were minimal. Buprenorphine treatment significantly reversed the P300 amplitude decrement following detoxification, whereas placebo-treated subjects continued to show depressed P300 amplitudes. These data demonstrate that buprenorphine treatment is effective in eliminating detoxification-induced impairments in one measure of cognitive ability.

Adult↗

PubMed1996

Sex differences in plasma cocaine levels and subjective effects after acute cocaine administration in human volunteers.

Gender differences after acute cocaine administration have received little attention in spite of the fact that males and females respond differently to many drugs. Seven male and seven female occasional cocaine users received both an intranasal dose of cocaine hydrochloride (0.9 mg/kg) and placebo powder in a randomized order and reported subjective effects via an instrumental joystick device and various questionnaires. Blood samples were withdrawn at 5-min intervals to assess pharmacokinetic differences. Male subjects achieved the highest peak plasma cocaine levels (144.4 +/- 17.5 ng/ml), detected cocaine effects significantly faster than females and also experienced a greater number of episodes of intense good and bad effects. Women studied during the follicular phase of their menstrual cycle had peak plasma cocaine levels of 73.2 +/- 9.9 ng/ml, which was significantly higher than when they were studied during their luteal phase (54.7 +/- 8.7 ng/ml), but there were no differences in their subjective reports of cocaine effects. In spite of the different cocaine blood levels and subjective effects, peak heart rate increases did not differ between males and females suggesting that women may be more sensitive than males to the cardiovascular effects of cocaine. These data suggest that there are significant gender and menstrual cycle differences in the response to acute intranasal cocaine administration and these differences may have implications for the differential abuse of this drug.

Administration, Intranasal↗

PubMed1996

Fluoxetine-induced sleep disturbance in depressed patients.

Abnormal polysomnographic (PSG) features, most notably increased electromyographic (EMG) tone and eye movements during non-REM sleep have been observed during sleep in fluoxetine-treated depressed patients. However, the relationship between these PSG features and sleep disruption is unclear. Nine depressed patients treated with 10 to 80 mg of fluoxetine and six unmedicated, depressed patients were studied polysomnographically on two consecutive nights during which sleep parameters, transient arousals, and eye movements were measured. The fluoxetine group experienced a lower-average sleep efficiency index (SEI) and significantly more eye movements and arousals during non-REM sleep than the control group. Eye movement and arousal counts were significantly correlated. In addition, clinically significant periodic limb movement disorder (PLMD) was observed in 44% of the fluoxetine-treated group versus none of the control group. We conclude that a higher incidence of PLMD and frequent transient arousals associated with eye movements may be responsible in part for the complaint of insomnia made by patients treated with fluoxetine.

Adult↗

PubMed1996

Are thyroid function tests necessary in patients with suspected sleep apnea?

Thyroid evaluation is frequently performed in patients with sleep apnea because of a suspected causal relationship between hypothyroidism and obstructive sleep apnea (OSA). The aim of this study was to determine the actual prevalence of hypothyroidism in patients referred for polysomnography and evaluate whether its rate was higher in patients with OSA than those without OSA. Ultrasensitive thyroid stimulating hormone (TSH) was performed on 255 of 279 consecutive patients referred for polysomnography from the neurology service of a large HMO. Hypothyroidism was detected in 1.6% (4/243) of all patients, 1.5% (3/194) of patients referred to evaluate OSA, and 2.0% of patients referred to evaluate the presence of periodic leg movement disorder (PLMD)/narcolepsy/parasomnia. There was no significant difference in rates of hypothyroidism in patients with documented OSA (2.9%, 3/103) compared to those without OSA (0.7%, 1/135). Two of the four patients with elevated TSHs had previously documented hypothyroidism and were on thyroxine replacement. Rates of hyperthyroidism were as high or higher than those of hypothyroidism in all groups. We conclude that thyroid screening does not appear to be appropriate for patients with suspected, or confirmed, OSA in the absence of signs or symptoms consistent with hypothyroidism or unless they are in a high risk group (women over the age of 60).

Adult↗

PubMed1996

An electromyographic marker for neuroleptic-induced akathisia: preliminary measures of sensitivity and specificity.

Previous polysomnographic (PSG) investigations have reported a rhythmic electromyographic (EMG) pattern (0.5-3.0 cps) of leg movement activity in a subset of patients with neuroleptic-induced akathisia (NIA). It has been suggested that this EMG pattern may represent a pathophysiological correlate of NIA and thus have clinical utility as an objective marker for this condition. We present preliminary measures of sensitivity and specificity for this EMG pattern as a diagnostic marker for NIA for 26 neuroleptic-treated patients. The EMG marker yielded a diagnostic sensitivity of 68.9% and a specificity of 70.0%, falling just short of statistical significance (Fisher's exact test p = 0.06). Quantitative analysis of the EMG pattern revealed a significant positive correlation between the percentage of time the NIA marker occurred during wakefulness and corresponding chlorpromazine equivalent levels. Clinical demographic findings for true-positive, false-positive, true-negative, and false-negative groups are discussed. Overall findings suggest that this particular pattern of EMG marker activity observed in neuroleptic-treated patients during PSG and EMG studies is valuable in facilitating the diagnosis and monitoring treatment.

Adolescent↗

PubMed1996

CNS effects and abuse liability of anabolic-androgenic steroids.

Anabolic-androgenic steroids (AAS) have become more widely used and abused not only by elite athletes, but by nonathletes as well. It appears that these drugs are being used for cosmetic purposes as well as for promoting aggressive behavior. However, AASs may also be used in combination with other drugs such as ethyl alcohol and cocaine--a practice that may contribute to the observed increase in aggressive behavior. As there are no reliable animal models of AAS self-administration, it has been difficult to characterize the abuse liability and physical dependence potential of this class of drugs. A better understanding of neuroactive steroids, improved methods for assessing AAS abuse, and a revised interpretation of drug-seeking behavior is needed to develop improved treatment strategies for this emerging health-related problem.

Aggression↗

PubMed1996

Effects of passive body heating on the sleep of older female insomniacs.

The purpose of this study was to evaluate passive body heating (PBH) as a treatment for insomnia in older adults. Polysomnographic recordings of older adults routinely show an increase in sleep fragmentation and a substantial decrease in slow-wave sleep (SWS) consistent with complaints of "lighter" more disturbed sleep. An increase in body temperature in young adults early in the evening by way of PBH has been shown to produce an increase in SWS in the early part of the sleep period. In a crossover design, nine female insomniacs (aged 60-72 yr) participated in two consecutive nights of PBH, involving hot (40-40.5 degrees C) and luke-warm (37.5-38.5 degrees C) baths 1.5 hours before bedtime. Significant improvement in sleep continuity and a trend toward an increase in SWS occurred after hot baths. Results of subjective measures showed that subjects experienced significantly "deeper" and more restful sleep after hot baths. In addition, hot baths resulted in a significant delay of temperature nadir in comparison to baseline nights.

Adult↗

PubMed1995

Electroencephalographic correlates of marihuana-induced euphoria.

The present study was conducted to determine if there is a neurophysiological correlate of marihuana-induced good effects or euphoria. Three groups of 6 male occasional marihuana smokers were prepared for electroencephalographic (EEG) recording and smoked either placebo or marihuana cigarettes containing 1.26% or 2.53% delta 9-tetrahydrocannabinol (delta 9-THC) in a controlled laboratory setting. Using a continuously available non-verbal joystick device and a questionnaire, subjects reported changes in their subjective mood state while EEG activity was continuously recorded. Subjects reported multiple episodes of intense good effects or euphoria during the first 15 min after marihuana. These episodes of euphoria occurred while plasma delta 9-THC levels were rapidly rising. EEG alpha power during these discrete episodes of euphoria was significantly higher suggesting that these transient EEG changes may reflect a neurophysiological correlate of the reinforcing effects of marihuana.

Adult↗

PubMed1995

Increased aggressive responding in male volunteers following the administration of gradually increasing doses of testosterone cypionate.

The present study assessed the effects of supraphysiologic doses of testosterone on aggressive responding in a controlled laboratory setting. Eight male subjects received gradually increasing doses of testosterone cypionate (150 mg/week for two weeks, 300 mg/week for two weeks, and 600 mg/week for two weeks) or placebo using a double-blind, randomized, cross-over design. Subjects were tested both before and after the series of injections. During the experimental session subjects could press a button to accumulate points exchangeable for money (non-aggressive response) or press another button to subtract points from a fictitious opponent (aggressive response). Aggressive responding was instigated by subtracting points from the subject which was attributable to the fictitious opponent. Testosterone administration resulted in a significantly higher number of aggressive responding compared to placebo.

Adult↗

PubMed1995

Buprenorphine-induced alterations of cocaine's reinforcing effects in rhesus monkey: a dose-response analysis.

Buprenorphine reduces cocaine self-administration by rhesus monkeys, opiate- and cocaine-dependent men and polydrug abusers, but the mechanisms underlying these cocaine-opiate interactions are not well understood. In the present study, the effects of daily placebo or buprenorphine (0.1, 0.3 and 1.0 mg/kg) treatment on cocaine self-administration (0.001-0.3 mg/kg/inject) were examined in five cocaine-experienced rhesus monkeys. Saline and each of six cocaine doses were available in an irregular order. Responding for cocaine (or saline) and food was maintained on a second order FR4 (VR 16:5) schedule of reinforcement. During placebo treatment, the daily number of cocaine injections increased as the unit dose was increased and then decreased at higher doses. Cocaine doses that maintained the highest rates of responding during placebo treatment were more resistant to buprenorphine's effects. The typical increase in response rate during the first five cocaine injections of a session also was attenuated by buprenorphine. The ascending limb of the cocaine dose-response curve was shifted downward and approximately one log unit to the right during low-dose buprenorphine treatment (0.1 mg/kg/day). In contrast, individual response rates for food pellets were unaffected. We conclude that buprenorphine selectively decreases self-administration of some unit doses of cocaine at doses that have minimal effects on food-maintained responding.

Animals↗

PubMed1995

Buprenorphine treatment of refractory depression.

Opiates were used to treat major depression until the mid-1950s. The advent of opioids with mixed agonist-antagonist or partial agonist activity, with reduced dependence and abuse liabilities, has made possible the reevaluation of opioids for this indication. This is of potential importance for the population of depressed patients who are unresponsive to or intolerant of conventional antidepressant agents. Ten subjects with treatment-refractory, unipolar, nonpsychotic, major depression were treated with the opioid partial agonist buprenorphine in an open-label study. Three subjects were unable to tolerate more than two doses because of side effects including malaise, nausea, and dysphoria. The remaining seven completed 4 to 6 weeks of treatment and as a group showed clinically striking improvement in both subjective and objective measures of depression. Much of this improvement was observed by the end of 1 week of treatment and persisted throughout the trial. Four subjects achieved complete remission of symptoms by the end of the trial (Hamilton Rating Scale for Depression scores < or = 6), two were moderately improved, and one deteriorated. These findings suggest a possible role for buprenorphine in treating refractory depression.

Adult↗

PubMed1995

A primate model of polydrug abuse: cocaine and heroin combinations.

Abuse of cocaine-opiate combinations ("speedballs") reported clinically was simulated in a rhesus monkey model of simultaneous cocaine and heroin self-administration. The reinforcing effects of nine cocaine-heroin combinations (cocaine [0.001, 0.01 and 0.10 mg/kg per injection i.v.] and heroin [0.0001, 0.001 and 0.01 mg/kg per injection i.v.]) were evaluated for 10 days on a second-order fixed ratio of 4 (variable ratio of 16:S) schedule and compared with self-administration of cocaine and heroin alone. Dose-effect curves for cocaine-heroin combinations usually were similar to those for cocaine and heroin alone, and intermediate doses maintained equivalent high levels of drug self-administration. No toxic effects were observed. In drug discrimination studies, cocaine (0.004-1.3 mg/kg) substitution resulted in a dose-dependent generalization to the training dose (0.4 mg/kg i.m.) in all five monkeys. Heroin substitution (0.01-1.0 mg/kg i.m.) resulted in dose-dependent and complete generalization to cocaine in three of five monkeys. Heroin pretreatment (0.1-0.18 mg/kg i.m.) did not change the cocaine discrimination dose-effect curve. Pretreatment with an opiate antagonist, quadazocine (0.1 mg/kg i.m.), had no effect on the discriminative stimulus effects of cocaine but antagonized the cocaine-like discriminative stimulus effects of heroin. Pretreatment with a dopamine antagonist, flupenthixol (0.018 mg/kg), antagonized the discriminative stimulus effects of cocaine but did not affect the cocaine-like effects of heroin. These findings demonstrate the feasibility of maintaining self-administration of cocaine-heroin combinations and suggest that cocaine and heroin have similar reinforcing and discriminative stimulus effects in rhesus monkeys.

Animals↗

PubMed1995

Role of delta opioid receptors in the reinforcing and discriminative stimulus effects of cocaine in rhesus monkeys.

The role of delta opioid receptors in the self-administration and discrimination of cocaine by rhesus monkeys was evaluated using the delta opioid antagonist naltrindole and the delta opioid agonist BW373U86 [(+/-)-4-((alpha R*)-alpha-((2S*,5R*)-4-Allyl-2,5-dimethyl-1- piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide dihydrochloride]. In the self-administration studies, monkeys were trained to respond for food (1 g banana pellets) or cocaine (0.032 mg/kg/injection, i.v.) under a second-order FR4(VR16:S) schedule of reinforcement during multiple daily food and drug sessions. Substitution of saline or other unit doses of cocaine (0.001-0.1 mg/kg/injection) for the maintenance dose of cocaine yielded typical inverted-U shaped dose-effect curves relating unit dose of cocaine to the number of saline or drug injections per day. The unit dose of cocaine available during drug sessions had little effect on food-maintained responding. In the drug discrimination studies, monkeys were trained to discriminate 0.4 mg/kg cocaine (i.m.) from saline in a two-lever, food-reinforced drug discrimination task. Cumulative dosing with cocaine (0.004-1.3 mg/kg) produced a dose-dependent generalization to the training dose of cocaine without consistently altering response rates. Initial experiments with naltrindole (0.1-3.2 mg/kg, i.v. or i.m.) produced effects in some monkeys suggesting that naltrindole may have antagonized the effects of cocaine under both procedures. In the drug self-administration studies, treatment with at least one dose of naltrindole for 10 consecutive days decreased self-administration of a unit dose of cocaine at the peak of the ascending limb of the cocaine dose-effect curve (0.01 mg/kg/injection) in three of four monkeys. In the drug discrimination studies, treatment with at least one dose of naltrindole shifted the cocaine dose-effect curve 1/2 log unit to the right in two of four monkeys. However, naltrindole did not alter the effects of cocaine in all monkeys under either procedure. Furthermore, in the monkeys in which naltrindole was effective, the cocaine-antagonist actions of naltrindole were not replicable and were not monotonically related to dose. When the delta agonist BW373U86 (0.001-0.032 mg/kg/inj, i.v.) was substituted for cocaine in one monkey in which naltrindole decreased cocaine self-administration, BW373186 was not self-administered. In addition, BW373U86 (0.0032-0.32 mg/kg, i.m.) neither generalized to cocaine nor potentiated the effects of cocaine in the drug discrimination procedure. These results suggest that delta opioid receptors play, at best, a minor and inconsistent role in the reinforcing and discriminative stimulus effects of cocaine in rhesus monkeys.

Animals↗

PubMed1994

Effects of morphine, naloxone, buprenorphine, butorphanol, haloperidol and imipramine on morphine withdrawal signs in cynomolgus monkeys.

This study was conducted to characterize the opiate dependence potential of a number of opiate and non-opiate psychoactive drugs in morphine-dependent cynomolgus monkeys (Macaca fascicularis). In addition, the agonist/antagonist profiles of buprenorphine and butorphanol were directly compared. Six male cynomolgus monkeys were maintained on morphine (3.0 mg/kg, q.i.d.) for 6 months. On evaluation days, monkeys were scored for opiate withdrawal signs 18 h after the last dose of morphine. Single dose suppression studies were conducted by giving subcutaneous injections of morphine (3 or 6 mg/kg), naloxone (0.01, 0.05 or 0.1 mg/kg), buprenorphine (1, 3, 10, 30 or 100 micrograms/kg), butorphanol (0.01, 0.1, 1.0 or 3.2 mg/kg), haloperidol (0.01, 0.05 or 0.1 mg/kg), imipramine (2, 5 or 10 mg/kg) or saline and measuring the number and frequency of withdrawal signs that appeared over a 2-h period. In a separate precipitation experiment either saline or 0.01 or 0.1 mg/kg butorphanol was administered 2 h after the last maintenance dose of morphine. In the single dose suppression test, morphine completely suppressed most withdrawal signs while naloxone increased the severity of withdrawal. All doses of buprenorphine increased many withdrawal signs such as backward gait, rearing, chafing face, chain biting, vomiting, masturbation, and vocalizations after intimidation. Only a few signs were reduced, but the overall withdrawal scores were not significantly increased. Low doses of butorphanol suppressed some signs while the highest dose almost completely eliminated all withdrawal signs. Butorphanol also failed to precipitate opiate withdrawal, and actually reversed the signs present in the saline-treated monkeys. Imipramine and haloperidol had little effect on the morphine withdrawal syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Marihuana smoking increases plasma cocaine levels and subjective reports of euphoria in male volunteers.

The reasons why individuals use this combination are not entirely clear, however, it has been speculated that marihuana may potentiate cocaine's subjective effects. Five male recreational drug users provided informed consent and volunteered to participate in this study. Each subject participated on 3 different days, separated by at least 1 week. Subjects sat in an isolated chamber and were prepared with electrocardiographic (ECG) electrodes for heart rate monitoring and an IV catheter for blood withdrawal. After adapting to the experimental chamber, they smoked a marihuana cigarette containing either 0.004% (placebo), 1.24%, or 2.64% delta 9-tetrahydrocannabinol (THC). Thirty minutes later they received an intranasal dose of 0.9 mg/kg cocaine. On subsequent visits, the marihuana dose was varied on a random basis. Subjects continuously reported changes in their mood state via an instrumental joystick device and filled out visual analog scales. Marihuana-induced tachycardia was increased even more after cocaine. The duration of all marihuana- and cocaine-related positive subjective effects was unchanged when both drugs were given, but marihuana pretreatment significantly reduced the latency to cocaine effects, from 1.87 to 0.53 min, and decreased the duration of dysphoric or bad effects, from 2.1 to 0.5 min. Peak plasma cocaine levels were 122.8 +/- 26.6 ng/ml after placebo marihuana, but pretreatment with the high-dose marihuana resulted in a significant increase in peak cocaine levels (233.8 +/- 19.2 ng/ml) and the apparent bioavailability as determined by area under the curve (AUC) analysis. We conclude that marihuana-induced vasodilation of the nasal mucosa attenuates the vasoconstrictive effects of cocaine and thus increases its absorption.

Adult↗

PubMed1994

In vivo proton magnetic resonance spectroscopy of alcohol in rhesus monkey brain.

Brain alcohol was measured in rhesus monkeys (Macaca mulatta) by proton magnetic resonance spectroscopy (MRS) following acute nasogastric alcohol administration (0.8 g/kg). Monkeys were anesthetized with ketamine and xylazine. A 1.5 T whole body imager and a 3-inch surface coil were used to acquire TE 30 and 270 ms spectra from a 7.5 cc voxel localized with a stimulated echo (STEAM) sequence. Venous blood samples were collected during spectral acquisitions for gas chromatographic determination of temporally concordant blood alcohol levels (BALs). Acute alcohol administration did not alter the resonance areas of N-acetylaspartate/N-acetyl containing compounds (NAA), choline containing compounds, or total creatine. The NAA resonance was used as an internal standard to calculate approximate brain alcohol concentrations, which averaged 27 +/- 3% and 27 +/- 8% of temporally concordant BALs (T2-corrected TE 30 and TE 270 ms spectra, respectively). In addition to reconfirming results from prior studies finding incomplete detection of brain alcohol with MRS, these results demonstrate the feasibility of measuring brain alcohol in anesthetized nonhuman primates to examine relationships between alcohol exposure history and MRS-visibility of brain alcohol.

Animals↗