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Biomedical subjects

J Bergman

Publications and source records attributed to J Bergman.

At least 163 records · Page 9Linked to original sources
PubMed1989

Effects of cocaine and related drugs in nonhuman primates. II. Stimulant effects on schedule-controlled behavior.

The behavioral effects of cocaine were compared with those of several cocaine derivatives and structurally distinct drugs that inhibit monoamine uptake. Squirrel monkeys were trained to respond under a fixed-interval schedule of stimulus-shock termination, and dose-effect curves were determined by administering cumulative doses i.v. Among the cocaine congeners, (-)-cocaine, (+)-pseudococaine and 1 alpha H, 3 alpha, 5 alpha H-tropan-3-yl-3,5-dichlorobenzoate produced dose-related increases in response rate, whereas (-)-pseudococaine, (-)-benzoylecgonine and (-)-benzoylnorecgonine did not increase responding consistently over a 100-fold or greater range of doses. 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine, which selectively inhibits uptake of dopamine, and mazindol, methylphenidate, nomifensine and bupropion, which inhibit uptake of dopamine as well as other monoamines, had behavioral effects similar to those of cocaine. In contrast, desipramine and citalopram, which selectively inhibit uptake of norepinephrine and serotonin, respectively, produced only dose-related decreases in response rate. The results combined with previous studies demonstrate a close correspondence between the potencies of 15 different drugs for producing cocaine-like behavioral effects and for displacing specifically bound [3H]cocaine in caudate-putamen. These findings are consistent with the view that the behavioral effects of cocaine and related drugs are linked to their actions at specific cocaine recognition sites associated with the dopamine uptake system.

Animals↗
PubMed1988

Antiherpesvirus activity and mechanism of action of indolo-(2,3-b)quinoxaline and analogs.

The antiherpesvirus activity of 14 derivatives of indoloquinoxaline was tested. The most active was 2,3-dimethyl(dimethylaminoethyl)5H-indolo-(2,3-b)quinoxaline, also called B-220. The antiherpesvirus mechanism of B-220 was sought. The compound inhibited replication of herpes simplex virus type 1, cytomegalovirus, and varicella-zoster virus in tissue culture at concentrations of 1 to 5 microM, depending on the cell type used for assay and the amount of virus. Cellular toxicity was seen at a concentration of 10 to 30 microM, and antiviral activity in the human bladder cancer and human embryonic lung fibroblast cell lines tested was found at concentrations 3 to 15 times lower than the concentrations causing cellular toxicity. Viral DNA synthesis, as well as production of early and late viral proteins, was inhibited at 0.5 to 4.5 microM B-220, but viral DNA polymerases tested in vitro were not inhibited at these concentrations. There was no interaction with the pyrophosphate analog foscarnet, and no reversal of the antiviral activity of B-220 occurred with naturally occurring nucleosides. We conclude that the antiviral effect depends on the multiplicity of infection and may occur at the level of viral DNA synthesis and that no interference occurs with pyrophosphate analogs or nucleosides. The more potent activity against viral DNA than against cellular DNA may be caused by a true selectivity for herpesvirus DNA or by the higher metabolism of viral DNA in infected cells.

Acyclovir↗
PubMed1988

Effects of levorphanol and several kappa-selective opioids on respiration and behavior in rhesus monkeys.

The effects of the mu-selective opioid, levorphanol (0.03-1.0 mg/kg), and the kappa-selective opioids, U-50,488 (0.03-1.0 mg/kg), tifluadom (0.01-0.3 mg/kg), bremazocine (0.0003-0.01 mg/kg) and MR 2034 (0.001-0.03 mg/kg), on ventilation and on schedule-controlled behavior were studied in rhesus monkeys. In seated, unanesthetized monkeys prepared with a head plethysmograph, ventilation during exposure to 5% CO2 mixed in air was measured after cumulative doses of each drug. In other monkeys, effects on behavior were studied by administering cumulative doses preceding sequential periods of fixed-ratio responding. Levorphanol, tifluadom, bremazocine and MR 2034 produced dose-related decreases in minute volume, tidal volume and respiratory frequency. In contrast, U-50,488 had only minimal effects on ventilation over the range of doses studied. All drugs decreased fixed-ratio rates in a dose-related manner. Comparisons between their effects in behavioral and respiratory experiments differentiated levorphanol and MR 2034 from U-50,488, bremazocine and tifluadom. Doses of levorphanol or MR 2034 that decreased minute volume markedly had little effect on behavior. In contrast, bremazocine, tifluadom and U-50,488 had less pronounced effects on minute volume at doses that suppressed behavior markedly. Naltrexone (0.03-1.0 mg/kg) antagonized decreases in minute volume produced by levorphanol, MR 2034, bremazocine and tifluadom, and apparent pA2 values were similar for each naltrexone-agonist pair. When the effects of levorphanol (0.03-0.3 mg/kg) were determined in the presence of U-50,488 (0.3 mg/kg), tifluadom (0.1 mg/kg) or bremazocine (0.003 mg/kg), the levorphanol dose-effect curve was shifted approximately 3-fold to the left, suggesting that the effects of the drugs were additive.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1988

Behavioral effects of histamine H1 antagonists: comparison with other drugs and modification by haloperidol.

The behavioral effects of several histamine H1 antagonists were compared in groups of squirrel monkeys trained to respond under fixed-interval schedules involving response-produced shock or termination of a stimulus associated with shock. Low to intermediate doses of the conventional H1 antagonists chlorpheniramine (up to 3.0 mg/kg), diphenhydramine (up to 1.0 or 3.0 mg/kg), pyrilamine (up to 3.0 mg/kg) and tripelennamine (up to 0.3 or 1.0 mg/kg) produced dose-related increases in response rate under all conditions in which they were studied; higher doses either increased responding less or decreased it. In contrast, a wide range of doses of the novel H1 antagonists AHR 11325 (1.0-30.0 mg/kg), astemizole (up to 10.0 mg/kg) and loratadine (up to 17.0 mg/kg) usually had little effect on responding, although decreases in response rate accompanied by emesis were observed after the highest doses in some monkeys. Other H1 antagonists including phenindamine (0.03-17.0 mg/kg), promethazine (0.03-5.6 mg/kg) and terfenadine (0.1-10.0 mg/kg) had different effects in individual subjects (i.e., dose-related increases in response rate in some monkeys and either little change or dose-related decreases in responding in other monkeys). The dopamine uptake inhibitors cocaine (0.01-1.0 mg/kg) and bupropion (0.1-10.0 mg/kg) had behavioral effects similar to those of chlorpheniramine, diphenhydramine, pyrilamine and tripelennamine, whereas the muscarinic antagonist atropine (0.03-1.0 mg/kg), the serotonin 5-hydroxytryptamine/5-hydroxytryptamine antagonist cyproheptadine (0.03-1.0 mg/kg), the norepinephrine uptake inhibitor desmethylimipramine (0.03-3.0 mg/kg) and the benzodiazepine diazepam (0.3-30.0 mg/kg) produced only dose-related decreases in response rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Suppression of behavior by food pellet-lithium chloride pairings in squirrel monkeys.

Responding by squirrel monkeys was maintained under a 30-response fixed-ratio schedule of food presentation; during different sessions responding produced either sucrose-flavored or banana-flavored food pellets. Pre-session administration of doses of lithium chloride (LiCl) less than 3.0 mEq/kg did not alter rates of responding whereas pairing either type of pellet with post-session injections of 1.8 mEq/kg LiCl suppressed both lever pressing and consumption during subsequent sessions in which that pellet type was available. When post-session injections of LiCl were discontinued, responding recovered within 14 sessions. The suppression of responding, but not pellet consumption, was then reliably reproduced in each monkey by pairing post-session LiCl with the previously non-paired type of pellet. Pre-session administration of chlordiazepoxide (CDAP, 3.0-17.0 mg/kg) increased rates of suppressed responding in a dose-related manner, but did not increase pellet consumption. These data indicate that different mechanisms may be involved in the suppression of responding and the suppression of consumption of food by post-session injections of drugs. The suppression of responding by post-session injections of drugs in primates appears to be qualitatively similar to the suppression of responding by other noxious stimuli such as electric shock in that it is reversible, it can be reinstated by re-exposure to post-session drug injections, and it can be attenuated by pre-session administration of CDAP.

Animals↗
PubMed1986

Some behavioral effects of histamine H1 antagonists in squirrel monkeys.

Graded dose of the histamine H1 antagonists tripelennamine (0.1-3.0 mg/kg), promethazine (0.1-3.0 mg/kg), diphenhydramine (0.3-10.0 mg/kg) and chlorpheniramine (0.3-1.7 mg/kg) increased rates of nonsuppressed responding under a second-order schedule of food presentation to a maximum beyond which responding was increased less or decreased. In contrast, the H2 antagonist, cimetidine, had no effect or decreased responding at the highest doses studied (56.0-100.0 mg/kg). Intermediate doses of tripelennamine, diphenhydramine and promethazine also increased rates of food-maintained responding that were suppressed by electric shock. Maximal increases in rates of suppressed responding were comparable to those produced by effective doses of chlordiazepoxide (3.0-10.0 mg/kg). Under identical conditions, clozapine (0.1-1.0 mg/kg) increased responding to a lesser extent, and d-amphetamine (0.01-0.3 mg/kg) and cimetidine (3.0-100.0 mg/kg) either did not increase or, at the highest doses, only decreased rates of suppressed responding. Doses of tripelennamine and diphenhydramine that increased rates of nonsuppressed and suppressed responding also maintained self-administration in cocaine-trained squirrel monkeys under a second-order schedule of i.v. injection. Rates and patterns of responding maintained by tripelennamine and diphenhydramine were comparable to those maintained by cocaine and d-amphetamine under identical conditions. The results show that histamine H1 antagonists can have pronounced rate-increasing effects on nonsuppressed and suppressed behavior, and that they can serve as reinforcers in monkeys. These effects occur at doses that probably are greater than those required to saturate H1 sites of action in central nervous system and may not be mediated solely through histaminic mechanisms.

Animals↗
PubMed1985

The reinforcing properties of diazepam under several conditions in the rhesus monkey.

Diazepam self-administration was studied in rhesus monkeys under several conditions of availability. Lever-press responding was maintained in twelve monkeys under a fixed-ratio 10 (FR 10) schedule of IV cocaine or pentobarbital delivery in daily sessions of 1-3 h duration. Each of several doses of diazepam (0.012-0.4 mg/kg/infusion) or vehicle was periodically substituted for 5-14 consecutive sessions. Between each substitution, responding was maintained by the baseline drug (cocaine or pentobarbital). Another procedure was to decrease the response requirement for drug delivery to a fixed-ratio one (FR 1). In three of eleven monkeys studied under conditions of a cocaine baseline and the FR 10 schedule, responding was maintained by diazepam and was inversely related to dose. In each of five monkeys tested in a similar manner but with a pentobarbital baseline, at least one dose of diazepam maintained responding above vehicle levels. Three of these monkeys had previously failed to self-administer diazepam under the cocaine baseline condition. Subsequently when two of these monkeys were returned to the cocaine baseline, diazepam was not self-administered above vehicle levels. Under FR 1 conditions of substitution, vehicle and pentobarbital intake increased in each monkey tested and cocaine intake increased in two of four monkeys. Diazepam self-administration also increased but did not exceed vehicle levels under the FR 1 schedule. However, in two monkeys the number of diazepam infusions was increased compared to the FR 10 substitution condition. These results emphasize the importance of testing drugs under several conditions to determine their relative dependence potential.

Animals↗
PubMed1985

Behavioral effects of naloxone and nalorphine preceding and following morphine maintenance in the rhesus monkey.

The effects of morphine, naloxone, and nalorphine on responding maintained under a variable-interval schedule of food presentation were assessed in rhesus monkeys before and after successive periods of daily morphine maintenance (15.0 mg/kg/day SC). Withdrawal from morphine dependence was accomplished gradually following the first two maintenance periods and abruptly following the third period. Schedule-controlled responding was disrupted when morphine maintenance was abruptly discontinued but not when the maintenance dosage was gradually reduced to zero. Tolerance to the acute effects of IV morphine on responding developed during morphine maintenance and dissipated after daily injections were discontinued. The effects of IV naloxone and IV nalorphine following each period of morphine maintenance were generally similar to their effects in initial determinations. These data indicate that tolerance-producing regimens of repeated daily injections with morphine do not necessarily produce enduring changes in the effects of opiate antagonists on schedule-controlled behavior. Additionally, gradual withdrawal from morphine maintenance can minimize the behavioral disruptions that attend abrupt abstinence.

Animals↗
PubMed1985

Origin and voltage dependence of asparagine-induced depolarization in intestinal cells of Xenopus embryo.

The kinetics and voltage dependence of asparagine (Asn)-induced depolarization in endoderm cells from Xenopus laevis embryos were analysed using current-clamp techniques. The depolarization is assumed to reflect the activation of an amino acid membrane carrier; it is accompanied by a slight increase in membrane resistance and cannot be explained by only the electrogenic character of the Asn carrier. It is proposed that the Asn depolarization arises, at least in part, from the decrease of the permeability ratio PK/PNa indirectly associated with the Na-coupled amino acid uptake. At room temperature (20-23 degrees C) the Asn response develops according to a single exponential function whose time constant is correlated with the final level of depolarization. Both amplitude and rise time of the depolarization are sensitive to variations of membrane potential and changes in Asn or Na external concentrations. Lowering the temperature decreases the amplitude of the Asn depolarization and increases its rise time with a Q10 factor of two; the kinetics remain of the Michaelis-Menten type, with a marked decrease in delta Emax and no change in Km. When the holding potential is altered by depolarizing and hyperpolarizing currents, the Asn response varies according to a bell-shaped characteristic presenting an optimum near the normal resting level. Membrane depolarizations induced by Na/K-pump inhibitors or high external K concentrations reduce the size of the Asn response; repolarizing the cell by current injection does not reverse the inhibitory effect of external K ions. Hyperpolarizing the membrane with a K-free Ringer solution increases the amplitude of the Asn response. In all these cases a decrease in delta Emax accounts for the apparent voltage sensitivity of the carrier mechanism. When induced by alterations of [K]o, an additional change in Km is observed, suggesting a K/Na-competitive inhibition of the Asn carrier. The results are discussed in terms of the amino acid carrier and passive membrane properties. It is suggested that the outward K-electrochemical gradient contributes an additional source of energy to the Na-dependent Asn uptake.

Animals↗
PubMed1985

Interactions of indoles with specific binding sites for 2,3,7,8-tetrachlorodibenzo-p-dioxin in rat liver.

In order to identify some of the structural requirements for binding of indoles to the receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), we have investigated the capacity of various indoles to inhibit specific [1,6-3H]TCDD binding in rat liver cytosol, as analyzed by electrofocusing in polyacrylamide gel. Of these indoles, indolo[3,2-b]carbazole was the most active. The IC50 value for receptor binding of indolo[3,2-b]carbazole as well as for 2,3,7,8-tetrachlorodibenzofuran was 3.6 nM, whereas that of 5,6-benzoflavone was 26 nM. Both indolo[3,2-b]carbazole and 2,3,7,8-tetrachlorodibenzofuran competitively inhibited the binding of [3H]TCDD to the receptor. The well-known microsomal enzyme inducer 3,3'-diindolymethane did not interact significantly with the TCDD receptor. Previous concepts of structure-activity relationships for binding of chlorinated dioxins to the TCDD receptor fail to account for the receptor binding of unhalogenated aryl hydrocarbon hydroxylase inducers such as 5,6-benzoflavone. We have instead considered the true three-dimensional space occupied by some receptor ligands by means of a computer using crystallographic data as inputs. When the atomic van der Waals radii were included, all potent receptor ligands studied could be fitted into a rectangle of 6.8 X 13.7 A.

Animals↗
PubMed1985

Behavioral effects of selected opiates and phencyclidine in the nondependent and cyclazocine-dependent rhesus monkey.

Tolerance to the behavioral effects of selected opiate compounds (cyclazocine, ketocyclazocine, naloxone and the stereoisomers of N-allylnormetazocine) and phencyclidine was evaluated using cumulative dosing procedures in rhesus monkeys responding under a fixed-ratio (FR) schedule of food presentation. Initially, the i.v. injection of graded doses of each drug in 8-min time-out periods preceding sequential FR periods decreased responding after each time-out in dose-related fashion. Subsequently, daily administration of up to 11 mg/kg of cyclazocine led to an approximately 16 to 32-fold rightward shift in the dose-effect curves for cyclazocine and ketocyclazocine and an approximately 4-fold rightward shift in the dose-effect curves for phencyclidine and (+)-N-allynormetazocine. In contrast, the dose-effect curves for naloxone and (-)-N-allynormetazocine were generally unchanged or shifted leftward. Termination of daily cyclazocine administration produced signs of withdrawal which disappeared over several days in all monkeys. These included emesis, frequent aggressive display and disruption of schedule-controlled performance. Present results suggest that the rate-decreasing effects of racemic cyclazocine involve mechanisms distinct from those mediating the rate-decreasing effects of naloxone or (-)-N-allynormetazocine. The differing degrees of cross-tolerance produced to the rate-decreasing effects of ketocyclazocine and of phencyclidine and (+)-N-allynormetazocine also suggest that the latter compounds produce behavioral effects to some extent through mechanisms distinct from those through which ketocyclazocine is effective.

Animals↗
PubMed1984

Formation of imine derivatives between biologically occurring amines and oxo-steroids.

Various biologically occurring amines have been shown to react with 3-oxo-17-oxo and 20-oxo-steroids during solvent evaporation at room temperature to form a complex pattern of products in each case. Using aliphatic monoamines it was shown that imine derivatives are first formed which rapidly rearrange into yet unidentified compounds. The extent of the overall transformation of the oxo-steroid varied with the amine investigated. Thus histamine gave rise to a 95% conversion of 17 beta-hydroxy-4-androsten-3-one (testosterone), whereas epinephrine caused 5% transformation under the same conditions. Imine formation as an experimental error in studies on the biochemistry of steroids is suggested.

Amines↗
PubMed1982

Do postcard reminders improve influenza compliance? A prospective trial of different postcard "cues".

A randomized trial of various postcard reminder "cues" was performed to improve understanding of health-related behavior and to find better strategies for improving influenza vaccination compliance. Data were gathered on 283 high-risk patients (92 per cent response rate) who received: 1) a "neutral" cue simply announcing the availability of vaccine; 2) a "Health-Belief-Model" card written to take advantage of the association between certain health beliefs and vaccination behavior; 3) a "personal" card signed by the patient's physician; or 4) no postcard. The highest rate of vaccination occurred among recipients of the Health-Belief-Model postcard (51.5 per cent vs. 20.2 per cent for control, p less than 0.001). Linear logistic regression analysis found that age, prior vaccination history and experimental group had a significant effect on likelihood of being vaccinated. After adjusting for age and prior vaccination experience, the vaccination rate was found to be significantly higher for persons receiving the Health-Belief-Model postcard compared with persons receiving no postcard or a neutral postcard. We conclude that reminder postcards emphasizing elements of the health belief model may help increase vaccination rates.

Aged↗
PubMed1982

Characteristics of the residency interview process preferred by medical student applicants.

This study elucidates the characteristics of the interview day preferred by medical students applying to family practice residencies. Interviews and informal meetings with residents were regarded as being the most helpful, followed by interviews with the director or faculty. Perceptions of other components of the interview day are also described. October was the month most students preferred, and two interviews each lasting 20 to 30 minutes were considered ideal. Group interviews were regarded negatively. The results of this survey are generalizable to other residency programs and could be helpful in planning the interview day.

Attitude of Health Personnel↗
PubMed1981

Food deprivation and cocaine self-administration.

The effects of food deprivation on the self-administration of cocaine were assessed in three rhesus monkeys under different schedules of reinforcement. In one subject, decreasing body weight to 80% of free-feeding weight (ffw) resulted in increase response rates and number of cocaine infusions taken. The same effects were observed in a second subject when restricted food intake resulted in 88% ffw. When schedule contingencies limited the number of infusions available, reduction to 90% ffw in the third subject resulted in increased response rates. These data suggest that food deprivation can be a potent variable in responding maintained by cocaine self-administration.

Animals↗
PubMed1981

The effects of electric shock on responding maintained by cocaine in rhesus monkeys.

Under baseline conditions, responding was maintained by intravenous cocaine delivery (100 micrograms/kg/infusion) under a fixed ratio 10 schedule in three rhesus monkeys. During test sessions, the onset of each cocaine infusion was accompanied by a delivery of electric shock of pre-determined duration and intensity. At intermediate intensity levels, the electric shock delivery initially reduced cocaine maintained responding. Although test sessions were separated by at least three baseline sessions, adaptation to the punishing effect of shock occurred within five test sessions in each monkey. Adaptation did not occur at higher intensity levels which completely eliminated cocaine-maintained responding, even when this intensity was tested prior to intermediate intensity levels.

Animals↗
PubMed1981

Electrogenic responses induced by neutral amino acids in endoderm cells from Xenopus embryo.

1. Membrane potential measurements were carried out on endoderm cells from early Xenopus embryos in order to study neutral amino acid transport in non-excitable cells. 2. The electrical properties of the cell membrane were studied under normal conditions, then in the presence of various Na/K-pump inhibitors and at different Na, K and Cl concentrations in Ringer solution. Blockade of the Na/K-pump by ouabain, Li, cooling to 10 degrees C or low [Na]0 induces similar depolarizations of about 40 mV. 3. External application of various neutral L-amino acids induces reversible membrane depolarizations. The D-isomeric forms are found to be ineffective. The amino acid induced depolarizations are not accompanied by changes in membrane resistance. They do not show voltage dependence for potential changes of less than 40 mV. 4. The amino acid depolarization increases with increasing concentration and follows first order Michaëlian kinetics. Both the size and the time course of the amino acid depolarization depend on [Na]0. Increasing [Na]0 markedly increases the apparent affinity of the membrane receptor for amino acid. 5. Increasing [k]0 reduces the size of the amino acid response. Short exposures to either ouabain or Li do not alter the amino acid depolarization. However, p time course of the amino acid depolarization depend on [Na]0. Increasing [Na]0 markedly increases the apparent affinity of the membrane receptor for amino acid. 5. Increasing [k]0 reduces the size of the amino acid response. Short exposures to either ouabain or Li do not alter the amino acid depolarization. However, p time course of the amino acid depolarization depend on [Na]0. Increasing [Na]0 markedly increases the apparent affinity of the membrane receptor for amino acid. 5. Increasing [k]0 reduces the size of the amino acid response. Short exposures to either ouabain or Li do not alter the amino acid depolarization. However, prolonged exposure to pump inhibitors or marked alteration of the Na concentration gradient leads to a complete inhibition of amino acid responses. 6. The results are in good agreement with the notion that the amino acid induced responses reflect the activation of an electrogenic amino acid carrier, very likely co-transporting Na and amino acid.

Animals↗