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J B Appel

Publications and source records attributed to J B Appel.

At least 55 records · Page 3Linked to original sources
PubMed1982

Psilocybin as a discriminative stimulus: lack of specificity in an animal behavior model for 'hallucinogens'.

Fifteen rats were trained to discriminate between the tryptamine hallucinogen psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine; 1.0 mg/kg) and saline in a two-lever choice task. Dose-response and time-response curves were obtained. The psilocybin cue generalized to psilocin (the dephosphorylated congener of psilocybin) and to the prototypical indoleamine hallucinogen LSD, but not to the phenylethylamine hallucinogen mescaline. These results indicate that the hallucinogenic effects of these drugs in humans may not be identical with their discriminative stimulus functions in animals, and that these four compounds may not be members of a single drug class. The term 'hallucinogen' may thus be a misnomer in the context of drug discrimination studies in nonhumans.

Animals↗
PubMed1982

Drugs and visual perception: effects of LSD, morphine and chloropromazine on accuracy, bias and speed.

Ten pigeons were trained to discriminate between the intensities of two white lights (projected behind a center response "key") using a discrete trial procedure in which choice behavior involved pecking at red or green lights projected behind left or right side keys. LSD (0.02-0.08 mg/kg) did not alter the accuracy of the brightness discrimination (percent correct) although it did lower response speed and may have differentially affected spatial (position) bias. Morphine (2.5--10.0 mg/kg) decreased accuracy of discrimination as well as response speed and had greater effects on trials when the bright stimulus was presented than when the dim stimulus was presented. Chlorpromazine (7.5-3.0 mg/kg) lowered accuracy without significantly altering any other measure of performance.

Animals↗
PubMed1982

Analyzing mechanism(s) of hallucinogenic drug action with drug discrimination procedures.

Some of the advantages of using drug discrimination (DD) procedure to analyze the mechanisms of action of hallucinogenic and related drugs were illustrated by reviewing research with lysergic acid diethylamide (LSD). Because they ensure that drug-induced alterations in interoceptive "state" become biologically meaningful "cues," these procedures are reliable, robust, sensitive and specific. With reference to LSD, many DD experiments suggest: (1) that while hallucinogens substitute for (mimic) LSD (in rats), such substitution does not predict hallucinogenic potency (in humans) but does predict similarities in mechanism(s) of action; (2) the behavioral (in vivo) effects of LSD, unlike those of some of its congeners, are mediated primarily by central, serotonergic (5-HT) neuronal mechanism although LSD may also have (secondary) dopamine (DA) agonist properties; (3) both the locus and the nature of these LSD-5-HT interactions are unclear: cells arising from B-7, B-8 and B-9 regions of the dorsal-medial raphe may be involved; pretreatment with agents that deplete 5-HT and increase the stereospecific binding of 3H-LSD in vitro (p-chlorophenylalanine; 5,7-dihydroxytryptamine) enhance sensitivity to LSD in vivo.

Animals↗
PubMed1982

The role of dopamine and serotonin in the discriminative stimulus effects of lisuride.

The discriminative stimulus properties of the clinically important ergot derivative lisuride hydrogen maleate (LHM) were investigated by training groups of rats (13 per group) to discriminate either of three training doses of LHM (0.02, 0.08 or 0.32 mg/kg) from saline. Dose-response tests showed that the three LHM cues were specific to the dose used during training and the dose-response curve became more steep as the training dose increased. In substitution tests, the direct dopamine (DA) agonists apomorphine and lergotrile substituted for LHM and the potency order of the LHM-like effect (LHM greater than apomorphine greater than lergotrile) corresponded to previous electrophysiological and biochemical results. The indirect DA agonist d-amphetamine did not substitute for LHM. The direct serotonin (5-HT) agonists quipazine, MK-212 and 5-methoxy-N,N-dimethyltryptamine produced dose-dependent, but incomplete, substitution for LHM which covaried with LHM training dose. In antagonism tests, only drug capable of blocking DA receptors, haloperidol and methiothepin, attenuated the LHM cues; the 5-HT antagonists cyproheptadine, BC-105 and xylamidine were ineffective. These data indicate that the primary neuronal action mediating the discriminative stimulus effects of a wide range of LHM doses was direct activation of central DA receptors. The 5-HT agonist actions of LHM proved to be secondary in that 5-HT agonists substituted only partially for LHM and 5-HT antagonists failed to attenuate LHM cues.

Animals↗
PubMed1981

A neuropharmacological analysis of the discriminative stimulus properties of fenfluramine.

Rats were trained to discriminate fenfluramine (1.0 mg/kg) from saline in a two-lever drug discrimination task. The dose-response curve for this discrimination was orderly with an ED50 of about one-half of the training dose (0.52 mg/kg). In substitution tests, indirect (p-chloroamphetamine) and direct (quipazine, MK-212, lisuride) serotonin (5-HT) agonists substituted for fenfluramine. Since none of these compounds have been reported to be hallucinogenic and the potent hallucinogen LSD did not substitute completely, it was suggested that the discriminative stimulus properties of fenfluramine are not related to its ability to produce hallucinations in humans. The fenfluramine cue, like the quipazine cue, was antagonized by the 5-HT antagonists cyproheptadine and methiothepin. Unlike quipazine, fenfluramine was also partially antagonized by the 5-HT uptake inhibitor, fluoxetine, and the 5-HT synthesis inhibitor, p-chlorophenylalanine. Thus, the fenfluramine cue differs from that of quipazine in that it is mediated via indirect actions on 5-HT receptors. Since the indirect dopamine (DA) agonist d-amphetamine failed to substitute and the DA antagonist haloperidol failed to block the fenfluramine cue, a mediating role for DA was not indicated. Another indirect DA agonist, cocaine, substituted partially for fenfluramine, a result which paralleled that seen with fluoxetine. Both of these partial substitutions were reduced by cyproheptadine; therefore, it was concluded that these effects may be due to the common ability of cocaine, fluoxetine, and fenfluramine to inhibit 5-HT uptake.

Animals↗
PubMed1981

Lack of specificity of an animal behavior model for hallucinogenic drug action.

It has been proposed recently that the occurrence of drug-induced limb-flicking (LF) and abortive grooming (AG) in cats can serve as a viable animal behavior model for the actions of hallucinogens in humans. If this is the case, such behaviors should occur reliably following the administration of drugs that produce hallucinations in humans and should not occur after administration of other, non-hallucinogenic drugs--a hypothesis that was examined in the present experiment. The frequency of LF and AG were observed in 12 cats which were given a wide range of doses of the potent hallucinogen, d-LSD (0.01-0.16 mg/kg), as well as several other compounds. The results showed that three non-hallucinogenic agents which are related to LSD in various ways, the ergot derivative lisuride, the serotonin agonist, quipazine, and the dopamine agonist, apomorphine, significantly increased LF frequency. Lisuride and quipazine also caused AG. Cocaine did not elicit either behavior. Thus, it was concluded that the proposed model cannot be regarded as specific to hallucinogenic drugs. In addition, the frequency of these behaviors, as well as their reliability and robustness, were shown to be party dependent on the environment in which observation occurs.

Animals↗
PubMed1980

Effects of pentazocine and other opiates on shock detection in the rat: involvement of opiate and dopamine receptors.

The hypothesis that the antinociceptive effects of pentazocine, a mixed agonist-antagonist opiate of the benzomorphan class, are mediated by a dual opiate-dopaminergic mechanism was tested using a two-choice procedure in which rats were required to discriminate the presence or absence of shock. The results showed that pentazocine decreased shock sensitivity and speed of responding, effects that were qualitatively similar to those of morphine. However, while the antinociceptive effect of both pentazocine and morphine could be antagonized by opiate receptor blockage, that of pentazocine, but not of morphine, could also be antagonized by dopamine receptor blockade. Observations with levorphanol and phenazocine suggested further that dopamine, as well as opiate receptor agonism may be characteristic of the benzomorphans.

Animals↗
PubMed1980

The effect of serotonin depletion on the discriminability of LSD.

Nine groups of rats were trained to discriminate LSD (0.12 mg/kg) from saline in a two-lever, water-reinforced, drug discrimination procedure. After stable discriminative performance was obtained (>95% correct), groups were administered one of several treatments which lower the concentration of serotonin (5-HT) in brain: (1) 12.5, 25, 50, 100 or 200 microgram of 5,7-dihydroxytryptamine (5,7-DHT) intraventricularly (IVT); (2) 3 X 100 mg/kg of p-chlorophenylalanine (PCPA) intraperitoneally (IP); or (3) 20 mg/kg of p-chloroamphetamine (PCA) IP. Control rats received either IVT injections of 5,7-DHT vehicle or IP injections of PCA or PCPA vehicles. Beginning 12 days after treatment, lever preference following various doses of LSD was determined. The results indicated that only the 200 microgram dose of 5,7-DHT and PCPA caused a significant potentiation of LSD-lever responding at the 0.03 mg/kg dose of LSD while all treatments except 12.5 and 25 microgram of 5,7-DHT resulted in significant depletion of 5-HT. Moreover, amount of 5-HT and percent LSD responding following 0.03 mg/kg LSD were not significantly correlated. It was concluded that 5-HT depletion, per se, cannot account for supersensitivity to the behavioral effects of LSD.

5,7-Dihydroxytryptamine↗
PubMed1979

An analysis of some perceptual effects of morphine, chlorpromazine, and LSD.

Male albino rats were trained to detect either a pure tone or a weak footshock embedded in white noise by utilizing a discrete-trial two-choice, successive discrimination procedure. The effects of morphine, chlorpromazine (CPZ), and lysergic acid diethylamide (LSD) were then analyzed on several measures of performance. Morphine (2.5--10 mg/kg) produced a nonspecific decrease in accuracy of discrimination on trials when the stimulus was presented as well as on trials when no stimulus occurred. Morphine was also followed by dose-dependent decreased in speed to initiate trials and by increases in intersubject variability. CPZ (1.0--4.0 mg/kg) caused a decrease in accuracy only on no-stimulus trials and, like morphine decreased speed to initiate trials. LSD (0.04--0.16 mg/kg/ decreased overall accuracy in a nonspecific manner (i.e., when shock and tone discriminations were considered together) and decreased speed by producing periods of nonresponding.

Acoustic Stimulation↗
PubMed1979

Drugs and the discrimination of duration.

The effects of lysergic acid diethylamide (LSD), d-amphetamine (AMP), chlorpromazine (CPZ), and the most active isomer of marihuana (delta9 - THC) on timing behavior were analyzed with a two-choice, discrete trial procedure in which pigeons were trained to discriminate visual stimuli that differed with respect to duration ('long' vs. 'short'). LSD (0.01, 0.04, 0.16 mg/kg) decreased response speed (increased latency), but otherwise had no significant effects on performance of the discrimination. d-Amphetamine (1.0, 2.0, 4.0 mg/kg) increased perseveration of 'spatial bias' and, at a dose of 4.0 mg/kg, lowered response speed. This compound did not significantly alter accuracy (percentage correct). CPZ (7.5, 15.0, 30.0 mg/kg) significantly decreased accuracy and, at a dose of 30.0 mg/kg, significantly lowered speed; THC also decreased accuracy and lowered speed. Neither CPZ nor THC significantly altered perseveration.

Animals↗
PubMed1979

Drug effects on the performance of pigeons under a negative automaintenance schedule.

Pigeons were exposed to a negative automaintenance schedule in which food was delivered following brief key illumination only if the illuminated key was not contacted; contact of the lighted key prevented food delivery. All subjects emitted some responses under this procedure when drugs were not given. However, the number of responses was less than that which occurred under an automaintenance procedure in which food followed key illumination regardless of the bird's behavior. Under the negative automaintenance procedure, acute administration of atropine (0.01--0.1 mg/kg), d-amphetamine (0.4--1.6 mg/kg), and morphine (3,8--15 mg/kg) reduced in a dose-dependent manner the percentage of key illuminations in which subjects contacted the lighted key. Diazepam (1.0--6.0 mg/kg) increased the percentage of key illuminations during contact responses occurred.

Animals↗
PubMed1978

Effects of morphine and chlorpromazine on the detection of shock.

A discrete-trial, two-choice, 'yes-no' procedure was used to determine the extent to which the perceptual effects of compounds such as morphine and chlorpromazine (CPZ) can be attributed to drug-induced changes in ability to detect shock stimuli (sensitivity). Both morphine (4.0, 5.0, and 6.0 mg/kg) and CPZ (0.25, 0.50, and 1.0 mg/kg) significantly reduced accuracy and increased the times (i.e., lowered the speeds) to initiate trials and to make choice responses. The effects of morphine appeared to be somewhat greater than those of CPZ, particularly at the lowest shock intensity (0.05 mA). When compared to appropriate saline control days, morphine, but not CPZ, significantly reduced accuracy of discrimination on trials when shocks were presented, whereas CPZ, but not morphine, reduced accuracy on no-shock trials. The effects of morphine, but not of CPZ, on accuracy (both overall and on shock trials) decreased as shock intensity increased. The effects of shock intensity were generally inversely related to the effects of morphine and directly related to the effects of CPZ.

Animals↗
PubMed1978

LSD and 5-HTP: tolerance and cross-tolerance relationships.

Tolerance and cross-tolerance relationships between lysergic acid diethylamide (LSD) and 5-hydroxytryptophan (5-HTP) were studied in rats trained on an operant task. The results demonstrated that behavioral tolerance to both compounds occur in the rat and that asymmetrical cross-tolerance relationships exist; that is, animals tolerant to 5-HTP were cross-tolerant to LSD, but animals tolerant to LSD were not cross-tolerant to 5-HTP.

5-Hydroxytryptophan↗
PubMed1978

Effects of opiates on the discriminative stimulus properties of dopamine agonists.

Two groups of rats were trained to discriminate the dopamine agonists amphetamine (0.75 mg/kg) or apomorphine (0.38 mg/kg) from saline in a two-lever operant task. Various doses of morphine and pentazocine were tested for generalization to and interference with the discriminative stimulus complexes produced by the dopamine agonists. Low doses of morphine appeared to produce a stimulus complex which is similar to that produced by apomorphine, but which differs from the produced by amphetamine. Pentazocine showed no evidence of generalization to either the apomorphine or the amphetamine cue. Neither opiate interfered with discriminative stimuli produced by the dopamine agonists, although decreases in the number of animals responding occurred.

Amphetamine↗