Search PubMed⌕ Search

Biomedical subjects

J H Mendelson

Publications and source records attributed to J H Mendelson.

At least 109 records · Page 6Linked to original sources
PubMed1990

Buprenorphine and naltrexone effects on cocaine self-administration by rhesus monkeys.

The effects of daily treatment with buprenorphine (0.237-0.70 mg/kg/day), naltrexone (0.32-3.20 mg/kg/day) and saline on cocaine self-administration were compared in rhesus monkeys. Cocaine (0.05 or 0.10 mg/kg/injection) and food (1-g banana pellets) self-administration were maintained on a fixed-ratio 4 (variable ratio 16:S) schedule of reinforcement. Buprenorphine, naltrexone or an equal volume saline control solution were infused slowly over 1 hr through one lumen of a double lumen i.v. catheter at the same time each day. Saline and each dose of buprenorphine (0.237, 0.40 and 0.70 mg/kg/day) or naltrexone (0.32 and 3.20 mg/kg/day) were studied for 60 sessions over 15 consecutive days. Buprenorphine significantly suppressed cocaine self-administration (P less than .001-.0001) in comparison to saline in all monkeys. Cocaine self-administration decreased by 49 to 95% in five of six monkeys on the 1st day of buprenorphine administration (0.237 and 0.40 mg/kg/day) and remained suppressed by an average of 72 to 93% during buprenorphine treatment. After abrupt termination of buprenorphine treatment (0.237 and 0.70 mg/kg/day), cocaine self-administration remained suppressed for an average of 16 +/- 4.4 and 28 +/- 6.6 days, respectively. Buprenorphine (0.237 and 0.40 mg/kg/day) initially suppressed food self-administration in some monkeys (P less than .01), but tolerance developed to buprenorphine's effects on food-maintained responding whereas cocaine self-administration remained significantly suppressed. During treatment with 0.70 mg/kg/day of buprenorphine, food self-administration returned to or significantly exceeded (P less than .01) base-line levels in three animals. Daily patterns of food self-administration were not disrupted by buprenorphine treatment. Naltrexone (0.32 mg/kg/day) initially suppressed cocaine self-administration by an average of 28% over 15 days (P less than .0009). During high-dose naltrexone treatment (3.20 mg/kg/day), cocaine-maintained responding was suppressed by 25% over 15 days (P less than .01). Cocaine-maintained responding was not significantly changed by naltrexone in one of the five subjects. Food self-administration decreased by 24% (P less than .05) after 5 days of 0.32 mg/kg of naltrexone administration, then exceeded baseline levels during 3.20 mg/kg of naltrexone administration. These data suggest that buprenorphine decreases cocaine's reinforcing properties more effectively than naltrexone across the dose-range studied. Buprenorphine may be an effective pharmacotherapy for treatment of cocaine abuse as well as dual abuse of cocaine plus heroin.

Animals↗
PubMed1989

Buprenorphine suppresses cocaine self-administration by rhesus monkeys.

Cocaine abuse has reached epidemic proportions in the United States, and the search for an effective pharmacotherapy continues. Because primates self-administer most of the drugs abused by humans, they can be used to predict the abuse liability of new drugs and for preclinical evaluation of new pharmacotherapies for drug abuse treatment. Daily administration of buprenorphine (an opioid mixed agonist-antagonist) significantly suppressed cocaine self-administration by rhesus monkeys for 30 consecutive days. The effects of buprenorphine were dose-dependent. The suppression of cocaine self-administration by buprenorphine did not reflect a generalized suppression of behavior. These data suggest that buprenorphine would be a useful pharmacotherapy for treatment of cocaine abuse. Because buprenorphine is a safe and effective pharmacotherapy for heroin dependence, buprenorphine treatment may also attenuate dual abuse of cocaine and heroin.

Animals↗
PubMed1989

A microanalysis of ethanol-induced disruption of body sway and psychomotor performance in women.

Measures of body sway, psychomotor performance and subjective reports of intoxication were obtained from 20 women after consuming either ethanol (0.56 g/kg) or placebo. Simple motor tasks were unaffected by the relatively low ethanol dose. Performance on the Digit Symbol Substitution Test (DSST) was affected only during the ascending portion of the blood ethanol curve while stance stability was disrupted during peak and descending blood ethanol levels. A microanalysis of the dynamic changes of ethanol-induced body sway was conducted and the results plotted in three-dimensional space. These data revealed that disruption of stance stability was more pronounced in the sagittal plane than in the lateral plane and that subjects swayed to the rear and the right side. The results of this study suggest that such data analysis techniques provide extremely sensitive measures of body sway resulting from consuming a moderate dose of ethanol.

Adult↗
PubMed1989

Naloxone suppresses buprenorphine stimulation of plasma prolactin.

The effects of parenterally-administered buprenorphine and simultaneous injection of naloxone was evaluated in six healthy adult males. Each subject was studied on six occasions, an average of 10 days apart, and received either two simultaneous intramuscular injections of saline, buprenorphine 0.3 mg and saline, or buprenorphine 0.3 mg and 0.6 mg, 0.45 mg, 0.3 mg, or 0.15 mg of naloxone. Simultaneous injection of buprenorphine 0.3 mg and saline resulted in an average increase in plasma prolactin above baseline levels of approximately 10 and 25 ng/ml, 30 and 55 minutes after injection. Buprenorphine-induced stimulation of plasma prolactin levels was statistically significantly greater than basal prolactin values (p less than 0.01). When 0.6 mg of naloxone was simultaneously injected with 0.3 mg buprenorphine, peak plasma prolactin levels were significantly lower (p less than 0.05) than prolactin values after administration of 0.3 mg buprenorphine and saline. Simultaneous injection of 0.45 mg naloxone and 0.3 mg buprenorphine also resulted in a significant attenuation (p less than 0.05) of buprenorphine-stimulated prolactin levels. Injection of 0.3 mg or 0.15 mg of naloxone did not inhibit prolactin stimulation produced by buprenorphine 0.3 mg. These findings demonstrate a dose-effect relationship between naloxone concentration and suppression of the increase in plasma prolactin levels produced by administration of buprenorphine 0.3 mg. As prolactin stimulation occurs shortly after opioid agonist administration and is temporally concordant with the rapid induction of pharmacologic reinforcement associated with opiate abuse, naloxone added to buprenorphine parenteral preparations may reduce the abuse potential of buprenorphine.

Adolescent↗
PubMed1989

Neuroendocrine consequences of alcohol abuse in women.

Alcohol abuse and alcoholism are associated with a broad spectrum of reproductive system disorders. Amenorrhea, anovulation, luteal phase dysfunction, and ovarian pathology may occur in alcohol-dependent women and alcohol abusers. Luteal phase dysfunction, anovulation and persistent hyperprolactinemia have also been observed in social drinkers studied under clinical research ward conditions. The mechanisms underlying alcohol-related disruptions of the hypothalamic-pituitary-ovarian-adrenal axis are unknown. The reproductive consequences of alcohol abuse and alcoholism range from infertility and increased risk for spontaneous abortion to impaired fetal growth and development. Recent studies of alcohol's effects on pituitary gonadotropins and on gonadal, steroid and adrenal hormones in women are reviewed. Research on the acute effects of alcohol on opioid antagonist and synthetic LHRH-stimulated pituitary gonadotropins is summarized. The implications of alcohol's effects on reproductive hormones for impairment of fetal growth and development are discussed.

Alcohol Drinking↗
PubMed1989

Cocaine effects on pulsatile secretion of anterior pituitary, gonadal, and adrenal hormones.

Pulse frequency analysis of LH, PRL, testosterone, and cortisol was carried out with the Cluster Analysis Program in eight male cocaine abusers and eight aged-matched normal men. Four of the eight cocaine abusers had hyperprolactinemia (range, 22.08-44.65 micrograms/L). Cocaine users as a group had significantly higher mean peak height (P less than 0.02) than control subjects. Cocaine users with hyperprolactinemia had higher mean peak height than control subjects or cocaine users with normal PRL levels (P less than 0.01). Cocaine users with hyperprolactinemia also had higher mean amplitude increments than control subjects (P less than 0.02). Cocaine users with hyperprolactinemia had a higher mean valley than controls (P less than 0.01) and cocaine users with normal PRL levels (P less than 0.03). However, there were no significant differences in PRL peak frequency, peak duration, or interpulse intervals between cocaine users with or without hyperprolactinemia and control subjects. There were minimal differences between cocaine users and control subjects in pulse frequency analysis of LH parameters; the small differences in mean LH levels and average interpulse interval were not in the abnormal range and were probably not biologically significant. No differences between cocaine users and controls were detected for pulse frequency analysis of testosterone or cortisol. Cocaine-induced hyperprolactinemia may contribute to disorders of sexual and reproductive function in men who abuse the drug, and recent reports that PRL modulates immune function suggest that cocaine-induced derangements of PRL secretion may also contribute to cocaine-related comorbidity in infectious disease. Since cocaine users with hyperprolactinemia had a higher mean valley as well as a higher peak pulse PRL height than control subjects, but did not have greater PRL pulse frequencies, we conclude that hyperprolactinemia in these men may be due to a cocaine-induced derangement of dopaminergic inhibition of basal PRL secretion.

Activity Cycles↗
PubMed1989

Topographic distribution of EEG alpha activity during ethanol-induced intoxication in women.

Topographic maps of brain electrical activity from scalp EEG electrodes were obtained from healthy adult female volunteers using a Brain Electrical Activity Mapping (BEAM) system. Each woman received both ethanol (0.7 g/kg, p.o.) and placebo in a counterbalanced order under double-blind conditions at an interval of 1-6 days. Subjective reports of intoxication were obtained continuously via an instrumental joystick device. Subjects reported when they detected ethanol and qualitatively pleasant (i.e., euphoric) or unpleasant (i.e., dysphoric) effects. All subjects reliably discriminated ethanol from placebo. Pronounced increases in EEG alpha activity occurred during ethanol-induced intoxication in all subjects. Analysis of topographic maps revealed that the distribution of high-amplitude, fast-frequency EEG alpha activity extended further frontally to the central sulcus and temporally during ethanol intoxication than during control sessions or after placebo administration. Area analysis and significant probability mapping techniques were used to quantify the increased alpha activity and to monitor changes during the process of intoxication in each individual. One woman, with a positive family history of alcoholism, experienced only a mild degree of ethanol intoxication. This behavioral response was accompanied by a slight decrease or no change in both slow- and fast-frequency alpha activity. This finding in a single subject provides additional evidence that a possible genetic predisposition for ethanol-related effects on behavior may be reflected in measures of brain electrical activity. Overall, these data also suggest that ethanol induces rapid and widespread increases in EEG alpha activity which may be associated with the reinforcing properties of ethanol.

Adult↗
PubMed1989

Alcohol, marijuana, and mood states in young women.

Potential predictors of 8 Profile of Mood States (POMS) factor scores were examined for 30 young women (mean age = 26.4 years). Prospective data were obtained from diary questionnaires and POMS ratings submitted daily during 3 consecutive menstrual cycles. Behavioral and social variables (heavy versus light marijuana smoking, consumption of both marijuana and alcohol on a given day, stress, and sexual activity) were stronger mood factor predictors than temporal or biological variables (weekends or menstrual cycle phase). Heavy marijuana users consistently reported higher negative moods and lower positive moods than light marijuana users.

Adult↗
PubMed1989

Alcohol effects on luteinizing hormone releasing hormone-stimulated anterior pituitary and gonadal hormones in women.

Plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, estradiol (E2) and progesterone were measured in 24 normal, adult women before and after i.v. administration of 100 micrograms luteinizing hormone releasing hormone (LHRH; Factrel) and p.o. ingestion of an alcohol (0.694 g of alcohol per kg b.wt.) or placebo solution. Twelve subjects were studied during the early follicular phase of the menstrual cycle and 12 subjects were studied during the midluteal phase of the menstrual cycle. During each menstrual cycle phase, six subjects received placebo solution and six subjects received alcohol solution administered under double-blind conditions. Mean peak blood alcohol levels of 113 to 122 mg/dl were measured 45 to 60 min after initiation of alcohol intake. LHRH stimulated a significant increase in LH after both alcohol (P less than .0001) and placebo (P less than .0001) administration, and this LH increase was equivalent during the follicular and the luteal phases of the menstrual cycle. LHRH also stimulated a significant increase in FSH levels after both alcohol and placebo intake during the follicular and luteal phases of the menstrual cycle (P less than .0001). There were no significant differences in LHRH-stimulated FSH between the alcohol and placebo conditions. Plasma prolactin levels also increased significantly after LHRH administration during the follicular and luteal phases of the menstrual cycle (P less than .0001). There were no significant differences in prolactin response to LHRH administration between the alcohol or placebo conditions during the follicular and luteal phases of the menstrual cycle. Plasma E2 levels did not increase significantly after LHRH administration and placebo alcohol during the follicular phase of the menstrual cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗