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Biomedical subjects

J D Leander

Publications and source records attributed to J D Leander.

At least 145 records · Page 8Linked to original sources
PubMed1977

Meperidine effects on schedule-controlled responding.

The effect of meperidine were studied on responding by pigeons under a multiple fixed-ratio, fixed-interval schedule of food presentation. Low doses of meperidine (0.3-3 mg/kg) generally increased and higher doses decreased responding under the fixed-interval component of the multiple schedule. The responding under the fixed-ratio component was usually unaffected by low doses and decreased by doses greater than 3 mg/kg of meperidine. Naloxone (1 mg/kg) antagonized the rate increases in the fixed-interval component; however, no dose of naloxone (1-56 mg/kg) or cyclazocine (0.1-3 mg/kg) antagonized the rate decreases produced by meperidine under either schedule component. The effects of morphine and meperidine were compared in two birds treated daily with methadone. In a bird maintained on a daily dose of 120 mg/kg (p.o.) of methadone, there was a 10-fold shift of the dose-effect curve for morphine but no shift of the meperidine dose-effect curve. In a bird maintained on a daily dose of 30 mg/kg (p.o.) of methadone, there was a 3- to 5-fold shift of the morphine dose-effect curve, but again no shift of the meperidine dose-effect curve. Thus, the rate-decreasing effects of meperidine were not antagonized by narcotic antagonists, nor did they show cross-tolerance to methadone.

Animals↗
PubMed1977

Toxic interactions of stimulants, narcotics and narcotic antagonists.

This study examines the lethality of combinations of central nervous system stimulants, narcotics and narcotic antagonists in rodents housed individually. The lethality of mice and rats from d-amphetamine was potentiated by methadone, cyclazocine and morphine, in that order of potency. Naloxone did not enhance lethality from d-amphetamine in mice, whereas it did antagonize lethality from morphine-d-amphetamine interactions. Naloxone did slightly enhance lethality from d-amphetamine in rats, but at a higher dose than those found to antagonize the lethality from morphine-d-amphetamine combinations. Methadone also enhanced the lethality from cocaine. These results have important implications for drug abusers and for patients being treated for narcotic addiction with either a methadone maintenance program or a cyclazocine administration program.

Animals↗
PubMed1976

Effects of naloxone and pentazocine on continuous shock-postponement responding by the pigeon.

The effects of pentazocine (3-30 mg/kg) and naloxone (3-100 mg/kg) were determined on the treadle-pressing behavior of pigeons under a schedule of shock postponement. Pentazocine increased the mean rate of responding at the 10 mg/kg dose, and greatly increased the mean shock rate at 30 mg/kg. Naloxone increased the mean response rate at all doses tested, without any increases in shock rates.

Animals↗
PubMed1976

Characteristics of ethanol drinking patterns under schedule-induced polydipsia.

Rats were induced to consume concentrations of ethanol between 5% and 10% (w/v) using the schedule-induced polydipsia technique. Although the substitution of ethanol solutions for water disrupted the usual post-pellet pattern of drinking, large amounts of ethanol were consumed and sound-induced convulsions were observed during ethanol withdrawal. In subsequent experiments, other rats chose 5% and sometimes 10% ethanol solutions over water where both water and ethanol were freely available during the first session of exposure to ethanol. Convulsions and wild running behavior could be observed in some of these rats after only 8 days of drinking, even though ethanol was freely available at all times. Use of the schedule-induced polydipsia technique served to bring the rats into early contact with the ethanol, but rats that received the same number of food pellets in a dish rather than by the schedule drank almost as much ethanol as did the rats receiving ethanol by the schedule. Rats with free access to food pellets drank very little ethanol.

Alcohol Drinking↗
PubMed1976

Ethanol and isopropanol effects on schedule-controlled responding.

The effects of ethanol and isopropanol were studied on responding by pigeons under multiple fixed-ratio (FR), fixed-interval (FI) schedules of food presentation and under a fixed-interval (FI) schedule of food presentation where responding was decreased by punishment. The ethanol was rapidly absorbed into blood and decreased responding within 15 min after intubation to the opening of the proventriculus. Dose-effect determinations of the effects of ethanol showed that ethanol decreased responding in both the FR and FI components of the multiple schedules at similar doses, but there were increases in responding under an FR 100 schedule at lower doses. Isopropanol tended to decrease FR responding at doses that either increased FI responding or did not affect FI responding. Both ethanol and isopropanol (1 g/kg) produced effects on the local rates of responding within the FI which were rate-dependent in that they increased low rates while not affecting or actually decreasing the high rates of responding. Both ethanol and isopropanol increased punished responding if it was not severely suppressed by the punishment procedures.

1-Propanol↗
PubMed1976

Schedule-induced oral self administration of etonitazene.

Rats were induced to drink either a saline-etonitazene solution or a saline solution with a schedule-induced polydipsia paradigm. When water was freely available, the rats continued to drink the saline solution or the saline-etonitazene solution, rather than the water. When the locations of the solutions were switched, the rats that were drinking saline switched to water (drank at the usual location), but the rats that were drinking saline-etonitazene continued to drink the saline-etonitazene solution (drank from the bottle at the other location). Naloxone administration temporarily eliminated the drinking of saline-etonitazene solution, but not that of saline solution.

Administration, Oral↗
PubMed1976

Interactions between naloxone and narcotic analgesics under three schedules that induce polydipsia.

A pattern of schedule-induced polydipsia was maintained in rats by a fixed-time schedule where food pellets were presented every 90 sec, a fixed-interval schedule where licking the drinking tube produced pellets every 90 sec, or a fixed-interval schedule where lever presses produced pellets every 90 sec. Under all 3 schedules, injections of morphine, methadone, etonitazene and meperidine generally decreased licking rates and amounts of water consumed, as well as rates of lever-pressing under the schedules where lever presses were required. Naloxone (1 mg/kg) almost completely blocked the effects of morphine and etonitazene, but the effects of methadone sometimes were blocked to a lesser degree. Small increases in the rate of licking and amount of water consumed after the lowest dose of meperidine under the schedule requiring lever-presses were blocked by naloxone, but the higher doses of meperidine that decreased licking, lever-pressing and amount of water consumed under the three schedules were not blocked by naloxone. These data suggest that there are important differences in the ability of naloxone to antagonize the behavioral effects of different narcotic analgesics.

Animals↗
PubMed1976

Effects of promazine, chlorpromazine, d-amphetamine, and pentobarbital on treadle pressing by pigeons under a signalled shock-postponement schedule.

The effects of promazine on treadle pressing to postpone the presentation of electric shock were studied in three pigeons. The effects of chlorpromazine, d-amphetamine, and pentobarbital were studied in two of these pigeons. Each treadle press postponed electric shock for 20 sec and presentation of a preshock stimulus for 14 sec. Selected doses of both promazine and chlorpromazine increased the rates of treadle pressing in all birds. The response-rate increases produced by promazine and chlorpromazine were due to increased conditional probabilities of treadle pressing both before and during the preshock stimulus. d-Amphetamine (1 and 3 mg/kg) slightly increased responding in one of the birds, but not to the extent that promazine or chlorpromazine did. In the other bird, the 10 mg/kg dose of d-amphetamine increased shock rate but did not change response rate. Some doses of d-amphetamine increased the conditional probabilities of responding both in the absence of the preshock signal and during the preshock signal in both birds. Pentobarbital only decreased response rates and increased shock rates.

Animals↗
PubMed1976

Effects of d-amphetamine, pentobarbital, chlorpromazine and promazine on electric shock postponement responding by the pigeon.

The effects of d-amphetamine, pentobarbital, chlorpromazine and promazine on responding under schedules of electric shock postponement were studied in pigeons. Responding was maintained by three different response-shock intervals (10, 20 and 60 seconds). Low doses (0.3-3 mg/kg) of d-amphetamine increased response rates without decreasing shock rates under all three response-shock intervals. The highest dose (10 mg/kg) of d-amphetamine increased the shock rates under all response-shock intervals and decreased the high response rate under the 10-second response-shock interval but did not decrease the lower rates of responding under the 20- and 60-second response-shock intervals. Pentobarbital decreased the high rate of responding maintained under the 10-second response-shock interval at lower dose (10 mg/kg) than the lower rates of under the 20- and 60-second response-shock intervals. The high dose (17.5 mg/kg) of pentobarbital decreased responding and the low doses (1-3 mg/kg) had no effect under all three response-shock intervals. Chlorpromazine (3-100 mg/kg) did not affect the average rate of responding under all response-shock intervals and only slightly increased shock rates under the 20- and 60-second response-shock intervals. Promazine (3-30 mg/kg) increased the rates of responding and decreased shock rates under all three response-shock intervals. Analysis of the temporal patterns of responding within the response-shock interval showed that d-amphetamine tended to induce the animals to respond earlier than they normally would in the response-shock interval while otherwise maintaining the temporal pattern of responding, pentobarbital decreased the probability of responses late in the response-shock interval, and chlorpromazine and promazine increased the probability of responses in the middle of the response-shock interval, producing a lessening of the temporal patterning of responding within the response-shock interval.

Animals↗
PubMed1976

Oral ingestion of narcotic analgesics by rats.

Rats drank solutions of narcotic analgesics as the only drinking fluid available in their cages. Relative to their daily water intake before the drug solutions were introduced, the rats drank more etonitazene solution, less methadone solution, and about the same volume of morphine, meperidine and levorphanol solution as water, although some rats would not drink the higher concentrations of morphine (1.0 mg/ml), levorphanol (1.0 mg/ml) and methadone (1.0 mg/ml). When naloxone (1.0 mg/kg) was administered after 12 days of drinking the drug solutions, the severity of the abstinence syndromes based on scoring of symptoms and on weight loss was morphine greater than or equal to etonitazine greater than levorphanol greater than meperidine greater than methadone. The animals showing the most severe syndrome after naloxone usually consumed more drug solution than usual during the next 24 hours, so that body weights were normal at the end of the 24-hour period. Nonprecipitated abstinence was also studied in these rats by replacing the drug solutions with water 3 to 5 days after the naloxone injection. Rats that had been drinking morphine, etonitazene and levorphanol lost weight for 2 or 3 days and then began to regain their lost weight. In contrast, rats which had been switched from methadone and meperidine solutions to water gained weight rapidly. Morphine and etonitazene drinkers which had been switched to water drank a lesser volume of water than they had been drinking of drug solution whereas some ex-methadone drinkers drank more water.

Administration, Oral↗
PubMed1975

Drugs and punished responding. V. Effects of drugs on responding suppressed by response-dependent and response-independent electric shock.

A procedure was used where responses by a pigeon produced electric shock both to that pigeon (response-dependent shock) and to another pigeon (response-independent shock) working under the same schedule of food presentation. Both response-dependent and response-independent shock partially suppressed responding. Pentobarbital, chlordiazepoxide and ethanol increased responding suppressed by response-dependent shock, but only pentobarbital increased responding suppressed by response-independent shock. Morphine, d-amphetamine, chlorpromazine, doxepin, and pentazocine either had no effect, or further decreased rates of responding suppressed by response-dependent or response-independent shock.

Animals↗
PubMed1975

Schedule-induced oral narcotic self-administration: acute and chronic effects.

A pattern of lever pressing was maintained in rats by presenting a food pellet following the first lever press to occur after at least 90-seconds had elapsed (fixed-interval 90-second schedule of food presentation, FI 90-second). With a drinking solution available, a pattern of excessive postpellet drinking (schedule-induced polydipsia) developed and was used to induce rats to drink solutions containing varying concentrations of narcotics. During acute exposure to morphine HCl, morphine SO4 or methadone HCl in the drinking solution, drinking decreased as a function of increasing drug concentration (from 0.3-1 mg/ml), but the total dose of narcotic ingested increased as a function of increasing drug concentration. The highest average dose of morphine HCl consumed in tap water was 30 mg/kg within an hour session. When morphine HCl was presented in an isotonic saline solution, drinking was increased and the highest average dose of morphine HCl ingested was 60 mg/kg within an hour session. The use of an isotonic saline solution did not appreceiably enhance the ingestion methadone HCl (about 30 mg/kg/hr). After chronic exposure to drug solutions for daily 4-hour sessions, the doses ingested averaged between 150 and 250 mg/kg/4 hr for 1 mg/ml solutions of morphine HCl and morphine SO4. The stable pattern of drinking exhibited by rats on the 0.5 mg/ml morphine HCl solution was characterized by a dissociation of drinking from pellet presentation. Chronic exposure to methadone HCl solutions (1 mg/ml) produced less drinking and lower doses ingested (approximately 100 mg/kg) than was obtained with either morphine HCl or morphine SO4 at an equal concentration.

Administration, Oral↗
PubMed1975

Effects of narcotic agonists and antagonists on schedule-induced water and morphine ingestion.

A pattern of lever pressing and schedule-induced polydipsia was maintained in rats by a fixed-interval 90-second of food presentation. The effects of acute morphine, methadone, nalorphine, naloxone, pentazocine and cyclazocine were studied in control rats (morphine-free rats) and rats maintained on 200 mg/kg daily oral infections of morphine (morphine-maintained rats). The effects of morphine, nalorphine and naloxone also were studied in rats that were drinking a 0.5 mg/ml of morphine solution (morphine-drinking rats) in the experimental apparatus. All six drugs decreased drinking in the morphine-free rats. Pentazocine and naloxone increased lever-pressing rates in the morphine-free rats, while morphine, methadone, nalorphine and cyclazocine only decreased lever-pressing rates. In the morphine-maintained rats, the dose-effect curves for both lever-pressing and drinking measures were shifted to the left for naloxone, nalorphine, pentazocine and cyclazocine, indicating an increased sensitivity to the antagonists, while the dose-effect curves for morphine and methadone were shifted to the right, indicating that the morphine-maintenance regimen had produced tolerance to these drugs. Morphine and methadone injections increased drinking in the morphone-maintained rats, but none of the drugs increased lever-pressing rates in the morphine-maintained rats. In the morphine-drinking rats, morphine decreased lever pressing at doses that left licking rates unaffected. Since the effects of morphine in the morphine-drinking rats differed from those in the morphine-free rats or the morphine-maintained rats, the effects of morphine on the self-ingestion of morphine in the experimental setting cannot be attributed entirely to the schedule of pellet delivery or to the effect of chronic morphine dosing.

Animals↗
PubMed1975

Rate-dependent Effects of drugs. II. effects of some major tranquilizers on multiple fixed-ratio, fixed-interval schedule performance.

The effects of promazine, chlorpromazine, triflupromazine, prochlorperazine, trifluoperazine, perphenazine, fluphenazine, haloperidol, benzquinamide, tetrabenazine and chlorprothixene were determined on the rate of conditioned key pecking of pigeons under a multiple fixed-ratio 30, fixed-interval 5-minute schedule of food presentation. Chlorpromazine, prochlorperazine, perphenazine, chlorprothixene and tetrabenazine decreased responding relatively more within the fixed-interval component than within the fixed-ratio component and also produced rate-dependent effects within the fixed interval component, increasing the low rates of responding early in the fixed-interval but decreasing the high rates of responding in the terminal parts of the fixed interval. Triflupromazine, trifluoperazine, fluphenazine and haloperidol also decreased responding relatively more within the fixed-interval component than within the fixed-ratio component, but did not produce rate-dependent effects within the fixed-interval component. Both low and high rates of responding within the fixed interval were decreased only by these four drugs and they produced small and inconsistent decreases in the quarter-life values. Promazine and benzquinamide decreased responding relatively more within the fixed-ratio component than within the fixed-interval component and also produced rate-dependent effects within the fixed-interval component. There was a structure-activity relationship between the chemical group on the benzene ring of the phenothiazine nucleus and the rate-dependent effect on responding within the fixed-interval component. Phenothiazines with a hydrogen or chlorine group on the benzene ring produced a rate-dependent effect on responding within the fixed interval, while phenothiazines with a trifluoromethyl group on the benzene ring did not produce a rate-dependent effect on responding within the fixed interval.

Animals↗
PubMed1973

Effects of food deprivation on free-operant avoidance behavior.

Lever pressing was maintained by Sidman's shock-postponement procedure and Herrnstein and Hineline's shock-frequency-reduction procedure with rats. Food deprivation to 80% and 70% of the animals' body weights on free feeding resulted in decreased response rates in both avoidance paradigms tested. Reinstatement of free-feeding conditions increased body weights and response rates and decreased shock rates. The effects of food deprivation were not dependent upon any particular avoidance parameters, or types, intensities, or durations of electric shock. These results mean that weight control is essential in long-term studies of avoidance behavior, and in studies of the effects on avoidance behavior of physiological interventions, such as hypothalamic lesions, that themselves may produce weight changes.

Animals↗
PubMed1973

Shock intensity and duration interactions on free-operant avoidance behavior.

Shock intensities (1 to 4 mA) and shock durations (0.3 to 0.75 sec) were concurrently varied over a range commonly used in free-operant avoidance studies using a lever-press response. Response rates were a positive linear function of the log of the product of intensity times duration. Shock rates were a negative linear function of that log. The increase in response rates was primarily due to a selective increase in the conditional probability of making responses with long interresponse times. The disproportionality of receiving shocks early in the session (warm-up) was also a linear function of the log of the intensity-duration product, with increasing disproportionality as the value of the intensity-duration product was increased. Thus, with all measures of the avoidance performance, shock intensity and shock duration combine in a multiplicative fashion to determine the avoidance performance.

Journal Article↗