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Biomedical subjects

J D Leander

Publications and source records attributed to J D Leander.

At least 109 records · Page 6Linked to original sources
PubMed1982

Effects of ketazocine, ethylketazocine and phenazocine on schedule-controlled behavior: antagonism by naloxone.

Dose-effect curves were determined for phenazocine (0.64-2.5 mg/kg), ketazocine (1.25-80 mg/kg) and ethylketazocine (1.25-80 mg/kg) in pigeons responding under a multiple fixed-ratio 30-response, fixed-interval 5-min schedule of grain presentation. All three opioid agonists decreased responding with the larger doses. The effects of phenazocine were completely antagonized by small doses of naloxone (0.01-1 mg/kg), whereas the effects of ethylketazocine required larger doses of naloxone (1-10 mg/kg) to be completely antagonized. The behavioral effects of ketazocine were partially attenuated by naloxone, but were not antagonized completely even by a 10 mg/kg dose of naloxone. These data from the pigeon are consistent with previous interpretations that the effects of phenazocine are mediated by actions at a mu opioid receptor, whereas the effects of ketazocine and ethylketazocine are mediated by actions at a kappa opioid receptor.

Analgesics, Opioid↗
PubMed1982

Meperidine-induced hypothermia in the rat.

A dose of 40 mg/kg of meperidine (pethidine) caused a marked lowering of rectal temperature in restrained female rats at room temperature (22 degrees C). This decrease was not antagonized by injection of 1 mg/kg of naloxone, whereas hypothermia of equal magnitude induced by 20 mg/kg of morphine was reversed by 1 mg/kg of naloxone. Pretreatment with the serotonin reuptake blocker, fluoxetine (10 mg/kg), or a non-hypothermic dose of meperidine (20 mg/kg) significantly potentiated the hypothermia induced by 100 mg/kg of l-5-hydroxytryptophan. The hypothermic effect of 40 mg/kg of meperidine was significantly greater than that of 10 mg/kg of fluoxetine. Finally, 40 mg/kg of meperidine produced a significantly greater hypothermic effect in restrained rats than in unrestrained rats. The results indicate that the hypothermic effect of meperidine is not a result of an opioid action, and that although it may be mediated through serotonergic systems, inhibition of serotonin reuptake is probably not the primary mechanism.

5-Hydroxytryptophan↗
PubMed1982

Interaction of diazepam with meperidine or normeperidine on analgesia and lethality.

The effects of meperidine and normeperidine were determined alone and after pretreatment with 10 mg/kg of diazepam on the tail-withdrawal measure of analgesia in rats. Lethal doses of normeperidine were determined alone and in combination with three doses of diazepam, and lethal doses of meperidine were determined along and in combination with 10 mg/kg of diazepam. Diazepam potentiated the analgesic effects of meperidine and increased the dose of normeperidine necessary to produce lethality.

Animals↗
PubMed1982

Effects of profadol on operant behavior in the pigeon.

The effects of profadol were determined on the key pecking of pigeons under the control of a multiple fixed-ratio, fixed-interval schedule of grain presentation. The effects of naloxone and pentobarbital on the behavioral suppression produced by profadol were also determined. Profadol (0.64-10 mg/kg) decreased responding under both schedule components, and the decrease in responding could not be reversed by either naloxone or pentobarbital. A moderate dose of profadol (1.25 mg/kg) was ineffective as an antagonist of morphine (20 mg/kg). Profadol does not produce its behavioral effects in pigeons by an action with a naloxone-sensitive opioid receptor and its non-opioid behavioral effects are dissimilar to those of previously studied meperidine-like phenylpiperidine analgesics.

Animals↗
PubMed1982

Effects of piribedil on schedule-controlled responding of the pigeon.

The effects of piribedil were studied in pigeons responding under a multiple fixed-ratio 30-response, fixed-interval 5-minute schedule of food presentation. Piribedil (0.03-10 mg/kg) increased responding under the fixed-interval component to a much greater extent than d-amphetamine (0.3-3 mg/kg) did. The rate-increasing effects of piribedil on fixed-interval responding were attenuated by haloperidol (0.003 and 0.03 mg/kg), alpha-methyl-p-tyrosine (50, 100 and 200 mg/kg), and tetrabenazine (10 and 30 mg/kg). These drug interactions suggest that piribedil acts as an indirect-acting, dopaminergic agonist to produce its rate-increasing effects on schedule-controlled responding in the pigeon.

Animals↗
PubMed1982

Comparison of phencyclidine, etoxadrol and dexoxadrol in the pigeon.

The effects of phencyclidine, etoxadrol and dexoxadrol were compared in pigeons responding under a multiple fixed-ratio 30-response, fixed-interval 5-minute schedule of grain presentation. Etoxadrol was half as potent as phencyclidine in suppressing responding, and dexoxadrol was half as potent as etoxadrol. These three drugs, along with ketamine and cyclazocine, were also compared in pigeons trained to discriminate injections of 0.64 mg/kg of phencyclidine from injections of distilled water. All five drugs produced phencyclidine-like responding at the higher doses, with the order of potency being phencyclidine, etoxadrol, cyclazocine, dexoxadrol and ketamine. These data showed that a phencyclidine-like discriminative cue can be demonstrated across three classes of chemical compounds, as exemplified by phencyclidine and ketamine, etoxadrol and dexoxadrol, and cyclazocine.

Analgesics↗
PubMed1982

Opioid and nonopioid behavioral effects of methadone isomers.

The effect of l-, d- and dl-methadone were determined on keypecking by pigeons under three different conditions: alone, in the presence of 1 mg/kg of naloxone and during daily administration of 60 mg/kg of dl-methadone. l-Methadone decreased responding at much lower doses than either dl- or d-methadone. Both naloxone and daily dl-methadone administration shifted l-methadone's dose-effect curves to the right until they could be superimposed over d-methadone's dose-effect curves. Doses of naloxone as low as 0.01 and 0.1 mg/kg shifted the dose-effect curves of l-methadone. Chronic daily administration of dl-methadone shifted the dose-effect curve for fentanyl to the right by 10-fold, whereas the effects of pentobarbital were slightly potentiated. These data indicate that l-methadone produces its effects by an interaction with an opioid receptor, whereas d-methadone's behavioral effects are produced by a nonopioid action. When the l-methadone-sensitive, opioid receptor is blocked by naloxone or tolerance has developed, than l-methadone can produce behavioral effects by a nonopioid mechanism. The tolerance produced by daily administration of dl-methadone in the pigeon is a result of cellular adaptation and not due to a drug dispositional mechanism.

Animals↗
PubMed1982

Effects of orally-administered ethanol and tertiary-butanol on fixed-ratio responding of rats.

Bar-press responding of rats was maintained under a 30-response fixed-ratio schedule of food presentation. Responding was characterized by an initial pause followed by a high rate of responding which prevailed until food delivery. Oral administration (15 minutes pre-session) of ethanol (0.25-6.0 g/kg) or tertiary-butanol (0.25-3.0 g/kg) produced dose-related decreases in responding at the higher doses; tertiary-butanol was 1.6 times as potent as ethanol. The 3.0 g/kg dose of ethanol or the 1.0 g/kg dose of tertiary-butanol decreased responding by about twenty percent when given either 15, 30, or 60 minutes prior to the experimental session. Overall response rate and response rate exclusive of the initial pause were decreased similarly.

Administration, Oral↗
PubMed1981

Clonidine analgesia and suppression of operant responding: dissociation of mechanism.

In the rat the effects of clonidine and xylazine were compared on a measure of analgesia (tail-withdrawal from hot water) and on operant responding maintained by a fixed-ratio 20-response schedule of food presentation. Clonidine (2--8 mg/kg) produced dose-dependent increase in tail-withdrawal latency and was approximately twice as potent as xylazine (8--16 mg/kg) in this test. This analgesic effect of 8 mg/kg of clonidine was antagonized by phenoxybenzamine (10 mg/kg), and high doses of yohimbine (5--10 mg/kg), whereas the effect of 2 mg/kg of clonidine was potentiated by a nonanalgesic dose of nisoxetine (10 mg/kg). Clonidine (0.0063--0.2 mg/kg) and xylazine (0.25--8 mg/kg) produced a dose-dependent suppression of fixed-ratio responding. The potency of clonidine in this task was approximately 40 times greater than that of xylazine. The suppression of responding produced by both drugs was antagonized by low doses of yohimbine (0.5--2 kg/mg), which was maximally effective at a dose of 1 mg/kg. The data suggest that when using this type of assay for analgesia, the antinociceptive effects of clonidine which are measured are a result of stimulation of alpha-adrenergic receptors or noradrenergic neurons or by adrenergic receptors which inhibit noradrenergic neurons.

Analgesics↗
PubMed1981

Effects of tetrabenazine and phenylpiperidine analgesics during daily clorgyline treatment.

Pigeons responded under a multiple fixed-ratio 30-response, fixed-interval 5-min schedule of food presentation. Daily administration of clorgyline (10 mg/kg, IM) tended to decrease rates of responding in both schedule components. Before daily clorgyline, tetrabenazine had no effect or decreased responding in the FI component at doses that markedly increased responding during chronic clorgyline. The clorgyline treatment resulted in a slight increase in sensitivity to the rate-decreasing effects of morphine, but no increased sensitivity to the rate-decreasing effects of meperidine, anileridine, alphaprodine, or fentanyl.

Analgesics↗
PubMed1981

Antagonism of oxotremorine-induced behavioral suppression by antimuscarinic drugs.

The effects of benztropine, scopolamine, atropine, methylatropine, amitriptyline, phencyclidine, and meperidine were determined alone and in conjunction with a behaviorally suppressing dose (0.05 mg/kg IM) of oxotremorine in pigeons responding under a multiple fixed-ratio 30 fixed-interval 5-min schedule of grain presentation. Benztropine, scopolamine, atropine, and amitriptyline antagonized the behavioral suppressing effects of oxotremorine at doses that alone decreased responding. In contrast, methylatropine, phencyclidine, and meperidine did not antagonize the effects of oxotremorine. These results suggest that benztropine, scopolamine, atropine, and amitripytline decrease responding due to an action at central muscarinic receptors, whereas the behavioral effects of methylatropine, phencyclidine, and meperidine are due to actions other than at central muscarinic receptors.

Animals↗
PubMed1981

Behavioral effects of phenylpiperidine narcotic antagonists.

The effects of three phenylpiperidines were studied in pigeons responding under a multiple fixed-ratio 30-response, fixed-interval 5-minute schedule of grain presentation. The first one studied was LY-27372 which as narcotic agonist analgesic effects but not antagonist activity. It decreased responding in both components and was not antagonized by naloxone. The two other drugs, LY-88329 and LY-99335, are tri-alkyl-4-phenylpiperidines which have narcotic antagonist activity. They decreased responding at doses of 5 and 40 mg/kg, respectively, when administered alone. When administered in combination with 20 mg/kg of morphine, they antagonized morphine's effects at 0.16 and 0.08 mg/kg respectively. A 10 mg/kg dose of pentobarbital attenuated the behavioral suppressant effects of 40 mg/kg of LY-99335, but not the suppressant effects of 5 mg/kg of LY-88329 or of 10 mg/kg of LY-27372. The data show that LY-99335 has a large separation between the doses which antagonized morphine and those which alone produce behavioral suppression by a proconvulsant effect at higher doses.

Animals↗
PubMed1981

Drug effects on multiple and alternating mixed-schedule performance.

The effects of d-amphetamine, pentobarbital, morphine, chlorpromazine and triflupromazine were determined on key pecking by pigeons maintained under multiple and alternating-mixed fixed-ratio 30, fixed-interval 5-min schedules of grain presentation. Similar schedule performances were maintained under both the multiple and alternating mixed schedules. The effects of d-amphetamine and pentobarbital were similar under the multiple and alternating mixed schedules. Low doses of d-amphetamine and pentobarbital increased relatively low rates of responding in the fixed-interval component and higher doses decreased rates of responding in both the fixed-interval and fixed-ratio components. The effects of morphine, chlorpromazine and triflupromazine on fixed-interval rates of responding did not differ between the multiple and alternating mixed schedules. However, morphine, chlorpromazine and triflupromazine decreased responding under the alternating mixed fixed-ratio without affecting responding under the multiple fixed-ratio component. This selective decrease in fixed-ratio responding under the alternating mixed schedule by morphine, chlorpromazine and triflupromazine appears to be functionally similar to the effects of these drugs to decrease avoidance responding without affecting escape responding.

Animals↗