Biomedical subjects

J E Barrett

Publications and source records attributed to J E Barrett.

At least 91 records · Page 5Linked to original sources

PubMed1986

Dihydropyridine calcium channel antagonists binding in non-mammalian vertebrates: characterization and relationship to 'peripheral-type' binding sites for benzodiazepines.

The densities of dihydropyridine calcium antagonist binding sites were examined in brains and cardiac issues of representative species from 4 classes of non-mammalian vertebrates (aves, pigeon; amphibia, frog; reptilia, chameleon; and osteichthyes, trout) previously shown to have low or undetectable levels of 'peripheral-type' binding sites for benzodiazepines. Dihydropyridine binding sites were present in brain and cardiac tissue of these 4 classes of non-mammalian vertebrates. The apparent dissociation constants for [3H]nitrendipine in non-mammalian vertebrates were comparable to those found in mammalian (rat) tissues. The densities of [3H]nitrendipine binding sites in brain and cardiac tissues were highest in the pigeon, with lower densities in tissues from chameleon, frog and trout. The densities of dihydropyridine binding sites in the latter tissues were comparable to those observed in the rat. Thus, dihydropyridine binding sites are phylogenetically diverse yet have similar kinetic characteristics in mammals and non-mammalian vertebrates. Despite the pharmacologic evidence that links dihydropyridine binding sites and peripheral binding sites for benzodiazepines in mammals, the earlier evolutionary appearance of the former sites suggest that even though they may share one or more common effector mechanisms, they are discrete entities.

Animals↗

PubMed1986

Antagonism of the behavioral effects of cocaine and d-amphetamine by prazosin.

Key pecking by pigeons was maintained under a 30-response fixed-ratio schedule of food delivery; lever pressing by squirrel monkeys was maintained under a 3-min fixed-interval schedule of food delivery. Administered alone, d-amphetamine (0.1-3.0 mg/kg), cocaine (1.0-3.0 mg/kg) and bupropion (1.0-30 mg/kg) either did not affect or decreased fixed-ratio responding of pigeons, whereas d-amphetamine (0.056-0.3 mg/kg) either increased or decreased (0.56 mg/kg) responding of monkeys maintained under the fixed-interval schedule. Prazosin, a selective centrally-active alpha 1 antagonist, produced a dose-dependent reversal of the rate-decreasing effects of d-amphetamine and cocaine but not of bupropion on fixed-ratio responding in pigeons. Prazosin also reversed both the rate-increasing and rate-decreasing effects of d-amphetamine on fixed-interval responding of squirrel monkeys. In contrast, the non-selective alpha-antagonist phentolamine enhanced d-amphetamine-induced decreases in fixed-ratio responding. These findings suggest that the behavioral effects of d-amphetamine and cocaine are produced at least in part by activation of central alpha 1 receptors. Prazosin may be a useful tool for better understanding the mechanisms through which cocaine, amphetamine, and other abused stimulant drugs exert their potent behavioral effects.

Animals↗

PubMed1986

Effects of MK-212 (6-chloro-2[1-piperazinyl]pyrazine) on schedule-controlled behavior and their reversal by 5-HT antagonists in the pigeon.

The effects of MK-212 (6-chloro-2[1-piperazinyl]pyrazine), a centrally-active 5-hydroxytryptamine (5-HT; serotonin) agonist, were studied alone and in combination with the 5-HT antagonists, methysergide (0.01-0.1 mg/kg), metergoline (0.01-1.0 mg/kg) and ketanserin (0.01-3.0 mg/kg). Pigeons were maintained under a procedure where key pecks were reinforced under a multiple fixed-interval (FI) fixed-ratio (FR) schedule of food presentation. In the fixed-interval component, the first response after 3 min had elapsed, produced food, while in the fixed-ratio component, the thirtieth response was reinforced. The drug MK-212 (0.1-3.0 mg/kg) produced dose-related decreases in response rates under both components of the schedule. In smaller doses of MK-212 (0.3 and 1.0 mg/kg), the decrease in the response rate was greater in the fixed-interval component than in the fixed-ratio component. Small doses of methysergide (0.03 mg/kg) and metergoline (0.1 mg/kg), which had little effect when given alone, partially blocked the effects of MK-212 (1.7 and 3.0 mg/kg) in decreasing rate. Larger doses of these compounds, which sometimes increased the response rate when given alone, resulted in a more complete restoration of response rates when administered with MK-212. Ketanserin, a selective 5-HT2 antagonist, reversed the effects of MK-212 in some cases, but the patterning of responses remained disturbed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

The antianxiety effect of beta-blockers on punished responding.

Clinically effective anxiolytic drugs generally increase responding that is suppressed by punishment. Although beta-adrenergic antagonists have been reported to reduce anxiety in humans, such effects have not been reported reliably in animal punishment procedures. In the present study, three pigeons were trained to key peck under a multiple schedule. In the presence of a white light every thirtieth response produced grain. In the presence of a red light every thirtieth response produced grain and electric shock which suppressed responding to approximately 10 percent of that occurring in the alternate component. Propranolol (1.0-5.6 mg/kg) and, less reliably, atenolol significantly increased punished responding in a dose-related manner; propranolol effects were approximately twice as large as those of atenolol. Both drugs no more than weakly increased unpunished response rates at doses that increased punished responding. These results suggest that beta-blockers have an antianxiety effect on punished behavior, and that peripheral beta-blockade, the predominant action of beta-blockers regardless of whether they readily penetrate the brain, is likely to be involved in this effect.

Adrenergic beta-Antagonists↗

PubMed1986

Benzodiazepine-like effects of inosine on punished behavior of pigeons.

Behavioral effects of the putative endogenous benzodiazepine receptor ligand, inosine, were studied alone and in combination with the benzodiazepine antagonist Ro 15-1788. Keypeck responses were maintained by food under a multiple fixed-interval 3-min, fixed-interval 3-min schedule of food delivery. Under the multiple schedule, the first response after 3 min produced food in the presence of either white (no punishment) or red keylights and, in addition, each 30th response produced a brief electric shock (punishment) when the keylight was red. Inosine increased the low rates of punished responding (10-100 mg/kg IM) and the higher rates of unpunished responding (30 mg/kg). The benzodiazepine antagonist Ro 15-1788 (0.03 mg/kg, IM) antagonized the rate-increasing effects of inosine but had no effect when given alone. Combinations of inosine (30 mg/kg) with higher doses of Ro 15-1788 (0.1-1 mg/kg) decreased responding much like Ro 15-1788 alone. The marked rate-decreasing effects of 1000 mg/kg inosine were not affected by concurrent administration of Ro 15-1788 (0.01-1 mg/kg). The behavioral effects of inosine alone resembled effects of benzodiazepines but not those of benzodiazepine antagonists. The response rate-increasing effects of inosine may be due to its benzodiazepine receptor binding properties, whereas the rate decreases produced by higher doses of inosine appear to be unrelated to benzodiazepine receptors.

Animals↗

PubMed1986

Differential antagonism of diazepam-induced loss of the righting response.

Ethyl-beta-carboline-3-carboxylate (beta-CCE), inosine and Ro 15-1788 are antagonists of several actions of the benzodiazepines. These compounds can be differentiated, however, according to their ability to reverse the loss of the righting response induced by diazepam. Ro 15-1788 completely reversed effects of diazepam on the righting response of pigeons and squirrel monkeys but was ineffective against comparable effects produced by pentobarbital. Pretreatment with Ro 15-1788 protected against diazepam-induced righting loss. Neither inosine nor beta-CCE reversed diazepam-induced righting loss or acted prophylactically against this effect. Since beta-CCE has been characterized as an inverse agonist at the benzodiazepine receptor, the absence of antagonism we report would suggest that beta-CCE lacks specific pharmacological activity which opposes suppression of the righting response by diazepam. Research with these preferentially-acting antagonists may lead to the development of anxiolytics devoid of the sedative-hypnotic properties inherent in the drugs currently in a clinical use.

Animals↗

PubMed1986

Interaction of buspirone and dopaminergic agents on punished behavior of pigeons.

The non-benzodiazepine anxiolytic buspirone was studied alone and in combination with either haloperidol or apomorphine. Drug effects were evaluated under a baseline of punished and unpunished keypeck responses of pigeons; every 30th response produced food (no punishment) in the presence of a white keylight and, when the keylight was red in alternate 3 min periods, every 30th response produced both food and a brief electric shock (punishment). Buspirone (0.03-3 mg/kg, IM) increased the low rates of punished responding to a maximum of 1000% of control at doses of 0.1-1 mg/kg. Unpunished responding was only marginally affected at lower doses and dose-dependent decreases were obtained from 1 to 10 mg/kg. Although less potent, chlordiazepoxide (1-100 mg/kg IM) produced effects which were similar to those of buspirone, a finding which contrasts with the greater efficacy of benzodiazepines for increasing punished behavior in mammals. Dose-effect functions for buspirone were unchanged by haloperidol administration (0.01 and 0.03 mg/kg, IM, 5 min prior) or by concurrent treatment with a behaviorally-ineffective dose of apomorphine (0.003 mg/kg, IM). Rate-decreasing doses of apomorphine (0.01-0.1 mg/kg) reversed the increases in punished responding produced by lower doses of buspirone (0.03 and 0.1 mg/kg) and the apomorphine-induced decreases in unpunished responding were antagonized by buspirone at doses which had little affect when given alone. The ability of buspirone to reverse the rate-decreasing effects of apomorphine on unpunished responding suggests that buspirone does exhibit dopaminergic antagonist properties in vivo. However, effects of buspirone on punished responding of pigeons do not appear to be due to dopaminergic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Performance evaluation of the Abbott HTLV III EIA, a test for antibody to HTLV III in donor blood.

An enzyme immunoassay (EIA), designed to detect antibodies to human T-cell lymphotropic virus type III (HTLV III), was evaluated. The antibody test was found to be highly sensitive; serum from 221 of 223 (99.1%) patients with acquired immune deficiency syndrome (AIDS) was positive for antibodies to HTLV III. In addition, the antibody test was found to be highly specific; approximately 99.75% of 20,720 serum or plasma samples from blood donors were negative for antibody to HTLV III. In most cases, the Western Blot analysis agreed well with the EIA. Eighty-one of 82 (98.8%) EIA-positive samples from patients with AIDS were Western Blot positive. Of the EIA-positive blood donors, 21 of 36 (58%) were detected and confirmed by Western Blot analysis. A solid-phase competitive EIA also was evaluated as an alternate procedure. The preliminary results indicate that this immunoassay has a high degree of sensitivity and specificity and could serve as an alternate procedure to detect antibody to HTLV III.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Drug-behavior interaction history: modification of the effects of morphine on punished behavior.

Squirrel monkeys were trained to respond under a multiple fixed-interval, fixed-interval schedule in which the first response after 5 min terminated a visual stimulus in the presence of which electric shocks could occur. During one component of the schedule, correlated with one color of stimulus lights, every 30th response also produced electric shock; responding was suppressed during this component to approximately 10 to 12% of that occurring in the alternate component in which responding was not punished. In contrast to previous research, morphine (0.03 to 1.0 mg/kg) increased punished responding. Unpunished responding, however, was either not affected or decreased at doses of morphine that increased punished responding. Increases in rate of punished responding also occurred when the single-schedule punishment condition was studied alone in these animals. Subsequent experimentation, which systematically analyzed the development of the rate-enhancing effects of morphine on punished responding, involved the study of drug effects in additional monkeys trained initially under a single-schedule punishment condition. The effects of morphine on punished responding were studied before, after, and then during exposure to the multiple schedule that included a component in which responding was not punished. Increases in response rate with morphine did not occur until it was administered during exposure to the multiple schedule that included a component in which responding was not punished. As with the other monkeys, once the rate increases in punished responding occurred under the multiple schedule, these effects of morphine persisted, even when the multiple schedule was removed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Behavioral studies with anxiolytic drugs. II. Interactions of zopiclone with ethyl-beta-carboline-3-carboxylate and Ro 15-1788 in squirrel monkeys.

The effects of zopiclone (0.1-100 mg/kg) were studied alone and in combination with the benzodiazepine receptor antagonist Ro 15-1788 and the inverse agonist ethyl-beta-carboline-3-carboxylate (beta-CCE). Under one procedure, food-maintained responding of squirrel monkeys was punished during one component of a multiple schedule. Each 30th response during both components produced food and, during the punishment component, also produced electric shock. Intermediate doses of zopiclone (0.3-30 mg/kg) did not affect or decreased unpunished responding and produced large increases in punished responding; higher zopiclone doses decreased responding under both conditions. beta-CCE (0.1-3 mg/kg) reversed both the rate-increasing and the rate-decreasing effects of zopiclone under each condition, producing a dose-dependent shift to the right of the zopiclone dose-effect curves. All doses of beta-CCE higher than 0.1 mg/kg decreased responding when given alone. Ro 15-1788 (0.1 or 1 mg/kg), which had no effect on punished or unpunished responding, reversed both the rate-increasing and the rate-decreasing effects of zopiclone. Under a second procedure, zopiclone increased responding of squirrel monkeys maintained by food under a 5-min fixed-interval schedule at doses that did not affect or decreased responding comparably maintained in an alternate component by response-produced electric shock. These effects were also reversed by both Ro 15-1788 and beta-CCE. When administered alone, beta-CCE produced effects opposite those of zopiclone and the benzodiazepines by decreasing responding maintained by food and increasing shock-maintained responding.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Behavioral studies with anxiolytic drugs. III. Antipunishment actions of buspirone in the pigeon do not involve benzodiazepine receptor mechanisms.

Buspirone, a clinically effective anxiolytic, has not shown robust effects consistently in procedures used traditionally with rodents and nonhuman primates to evaluate potential antianxiety activity. When key pecking by pigeons was maintained by food and was punished alternately under one component of a multiple schedule by the presentation of electric shock (conflict procedure), buspirone (0.03-10.0 mg/kg i.m.) produced increases in punished responding that were up to 30 times those of the control response rate. These doses did not affect or decreased unpunished responding. A buspirone analog, MJ 13805 (gepirone) produced effects similar to buspirone, although unpunished responding was slightly more sensitive to the rate-decreasing effects of MJ 13805 than to those of buspirone. A metabolite of buspirone, 1-pyrimidinyl piperazine (1-PP; MJ 13653), did not affect key pecking across a wide dose range (0.01-3.0 mg/kg i.m.), although slight decreases in both punished and unpunished responding occurred at the highest dose. Increases in punished responding with buspirone were not affected by the benzodiazepine receptor antagonist Ro 15-1788 (0.01-0.1 mg/kg i.m.). [3H]Diazepam binding to pigeon cerebrum or cerebellum in vivo was not altered by buspirone, or did buspirone, MJ 13805, or 1-pyrimidinyl piperazine displace [3H]flunitrazepam binding in vitro at pharmacologically relevant concentrations. These findings confirm previous work demonstrating marked rate-increasing effects of buspirone on punished responding in the pigeon, extend such effects to the buspirone analog MJ 13805 and indicate that the effects of buspirone are not mediated through the benzodiazepine receptor complex.

Animals↗

PubMed1985

Behavioral effects and benzodiazepine antagonist activity of Ro 15-1788 (flumazepil) in pigeons.

The selective benzodiazepine receptor antagonist, Ro 15-1788, produced behavioral effects in pigeons at doses at least 100 times lower than those previously reported to possess intrinsic pharmacological activity in mammals. In contrast to its effects in mammalian species, in pigeons, Ro 15-1788 does not exhibit partial agonist activity. Key-peck responses of pigeons were studied under a multiple fixed-interval 3-min, fixed-interval 3-min schedule in which the first response after 3-min produced food in the presence of red or white keylights. In addition, every 30th response during the red keylight produced a brief electric shock (punishment). Under control conditions, punished responding was suppressed to 30% of unpunished response levels. Ro 15-1788 (0.01 mg/kg, i.m.) increased unpunished response rates by 33% without affecting rates of punished responding. Doses of 0.1 to 1.0 mg/kg Ro 15-1788 produced dose-related decreases in both punished and unpunished responding. As is characteristic of other benzodiazepines, midazolam (0.1 and 0.3 mg/kg, i.m.) markedly increased punished responding but had little effect on rates of unpunished responding. Ro 15-1788 antagonized the increases in punished responding and also reversed the rate-decreasing effects of higher doses of midazolam. However, the effectiveness of Ro 15-1788 as a benzodiazepine antagonist was limited by its intrinsic activity: rate-decreasing doses of Ro 15-1788 were unable to completely reverse behavioral effects of midazolam. Midazolam was an effective antagonist of the behavioral effects of Ro 15-1788 (up to 0.1 mg/kg) but midazolam did not influence the rate-decreasing effects of 1.0 mg/kg Ro 15-1788 across a 100-fold dose range. In the pigeon, the behavioral effects of relatively low doses of Ro 15-1788 (0.01-0.1 mg/kg) appear to be related to benzodiazepine receptor mechanisms, whereas other systems appear to be involved in the effects of higher doses.

Animals↗

PubMed1985

Late evolutionary appearance of 'peripheral-type' binding sites for benzodiazepines.

Four classes of non-mammalian vertebrates were examined for the presence of both 'brain-specific' and 'peripheral-type' binding sites for benzodiazepines in the central nervous system. 'Brain-specific' binding sites for benzodiazepines were found in the central nervous systems of all non-mammalian vertebrates studied. However, in contrast to mammals, either very low or undetectable levels of 'peripheral-type' binding sites for benzodiazepines were observed in the central nervous systems of these non-mammalian vertebrates. Furthermore, the density of 'peripheral-type' binding sites for benzodiazepines in non-mammalian vertebrate heart was less than or equal to 2% of that found in mammalian cardiac tissue. These findings suggest a very late evolutionary appearance of 'peripheral-type' binding sites for benzodiazepines, implying that these sites may have (a) highly specialized function(s) in both peripheral tissues and the central nervous system.

Animals↗

PubMed1985

Interactions between the benzodiazepine receptor antagonist Ro 15-1788 (flumazepil) and the inverse agonist beta-CCE: behavioral studies with squirrel monkeys.

The effects of Ro 15-1788 and ethyl-beta-carboline-3-carboxylate (beta-CCE) were studied alone and in combination on the behavioral performances of squirrel monkeys. Under one procedure, performances maintained by food were suppressed by electric shock presentation (punishment or "conflict" procedure). Under a second procedure, responding was maintained either by food or electric shock delivery under a 5-min fixed-interval schedule. Doses of beta-CCE between 0.1 and 3.0 mg/kg, i.m., produced graded decreases in punished responding which were reversed by pretreatment with Ro 15-1788 (1.0 - 10.0 mg/kg, i.m.). Low doses of beta-CCE (0.03 - 0.3 mg/kg, i.m.) increased responding of monkeys maintained by shock presentation, but did not affect food-maintained responding; higher doses of beta-CCE decreased responding under both schedules. These effects of beta-CCE are opposite those produced by the benzodiazepines under this procedure. Ro 15-1788 (1.0 mg/kg i.m.) antagonized the effects of beta-CCE, producing a shift to the right in the dose-response curves. These findings provide further support for the view that beta-CCE and Ro 15-1788 produce effects mediated by the same benzodiazepine receptor recognition site.

Animals↗

PubMed1985

Evaluation of CMV total antibody EIA. An enzyme immunoassay for detection of antibodies to cytomegalovirus.

The performance of an indirect enzyme-immunoassay (CMV Total Antibody EIA, Abbott Laboratories) for the detection of the presence or absence of antibodies to cytomegalovirus (CMV) was evaluated by investigators at five clinical sites. The interassay and intraassay coefficient of variation data showed that the EIA could be performed in a highly reproducible manner at all sites. The investigators tested a total of 2314 clinical samples for antibody to CMV by the CMV Total Antibody EIA and by an indirect hemagglutination assay (IHA). The overall results demonstrated that compared with IHA the sensitivity of the EIA was 97.9% (1096/1120) and the specificity was 93.6% (1096/1171). The clinical samples tested included sera, plasma, and whole blood. These results show a good agreement between the CMV Total Antibody EIA and the IHA. This EIA is a simple, objective, and reproducible method for the detection of antibodies to CMV in sera, plasma, or whole blood samples, and the total procedure is adaptable for batching and automation and takes only 3 hr of elapsed time.

Antibodies, Viral↗

PubMed1985

Evaluation of the Spot-CAMP test for the rapid presumptive identification of group B streptococci.

A rapid Spot-CAMP test was evaluated for its ability to accurately identify colonies of Streptococcus agalactiae (Lancefield Group B) growing on primary sheep blood agar plates. The test uses a beta-lysin-containing filtrate, which is prepared from a broth culture of Staphylococcus aureus. A drop of beta-lysin filtrate is applied adjacent to a suspected group B Streptococcus (GBS) colony and the plate is incubated and then examined for a zone of synergistic hemolysis. The Spot-CAMP test demonstrated 100% correlation with both a Standard CAMP procedure and Lancefield serogrouping. The rapid Spot-CAMP test was easy to perform and inexpensive, and could presumptively identify within 30 minutes colonies of GBS growing on primary isolation plates.

Antimicrobial Cationic Peptides↗

PubMed1985

A urine preservative system to maintain bacterial counts. A laboratory and clinical evaluation.

The urinary tract is a common site of infection in the hospitalized, institutionalized, or ambulatory patient population. Ideally, urine should be cultured immediately or refrigerated up to 24 hours for quantitative examination for microorganisms. In the evaluation of patients at their homes or in long-term care facilities, rapid plating or refrigeration may not be practical. This is also true when evaluating small children in whom external collection devices are required to obtain a specimen. Because of these limitations, we evaluated a urine preservative and transport system, the Sage Products Urine Culture Tube, in a study of 1469 clinical specimens. This tube utilizes boric acid (1.1% final concentration) as a preservative. The Urine Culture Tube was easy to use and was as effective as refrigeration in maintaining bacterial counts. This system may be particularly useful where rapid transport or refrigeration is limited.

Bacteria↗

PubMed1985

Neuropeptide modulation of the behavioral effects of drugs.

Studies employing conditioned operant behavior of squirrel monkeys, rabbits and pigeons have demonstrated that the neuroactive peptides thyrotropin-releasing hormone (TRH), substance P (SP) and neurotensin (NT) produce marked behavioral effects under a wide range of procedures. These compounds appear to be particularly active when given in combination with other drugs. The co-administration of TRH with chlordiazepoxide, pentobarbital and ethanol potentiates the effects of these agents on punished behavior. Under other conditions SP can reverse the effects of chlordiazepoxide, whereas NT enhances the effects of haloperidol. Neither TRH, SP nor NT are behaviorally active at doses that produced significant interactions. These results support the view that neuropeptides exert modulatory effects on various neurotransmitter systems. An understanding of peptide-drug interactions should contribute to the development of new compounds with enhanced psychopharmacological efficacy and minimal side effects.

Animals↗