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Biomedical subjects

F C Colpaert

Publications and source records attributed to F C Colpaert.

At least 181 records · Page 10Linked to original sources
PubMed1977

Effects of alpha-methyl-p-tyrosine, adrenolytic compounds, pimozide and other neuroleptics, on the narcotic cue.

Using a two-lever food-reinforced operant procedure, rats (n=11) were trained to discriminate the narcotic analgesic fentanyl (0.04 mg/kg, s.c.) from saline. In rats so trained, alpha methyl-p-tyrosine (150 mg/kg, i.p.) was found not to affect the discriminability of fentanyl. Pretreatment (s.c.) with either adrenolytic compounds (10 mg/kg aceperone, 40 mg/kg dibenamine, 10 mg/kg phenoxybenzamine, 20 mg/kg propranolol) or sedative neuroleptics (0.63 mg/kg azaperone, 1.25 mg/kg chlorpromazine, 10 mg/kg pipamperone) likewise failed to attenuate the narcotic cue. Pimozide (0.63 mg/kg) and, to some extent, spiperone (0.04 mg/kg) reduced the percentage of responding on the selected lever, and pimozide antagonized drug lever selection in some animals. The results suggest that specific neuroleptics (e.g. pimozide) may affect the subjective effects induced by narcotics in humans.

Animals↗
PubMed1976

On the classification of antidepressant drugs.

Clinical, pharmacologic, and biochemical profiles of antidepressant drugs have been analyzed statistically. A method derived from multivariate statistics separates mere drug potency from the spectral information contained in the profiles. The dimensionality of the spectra is also reduced and this results in a diagram of associations and dissociations between the antidepressants and their scales of observation. The spectra of antidepressants show three poles which have been labeled as D (desipraminelike), A (amitriptylinelike), and M (MAOI). Clinical spectra agree better between one another than various pharmacologic spectra do. Monoamine oxidase inhibitors are readily differentiated from the tricyclic compounds. The latter appear in the sequence: desipramine, nortriptyline, imipramine, and amitriptyline. This sequence can also be reproduced from biochemical spectra of central and peripheral blockade of norepinephrine and serotonin reuptake.

Affect↗
PubMed1976

Theoretical and methodological considerations on drug discrimination learning.

A method is described which allows the assessment of discriminative stimulus properties of drugs, and the ability of amphetamine (0.16 mg/kg s.c.), chlordiazepoxide (5 mg/kg p.o.), desipramine (5 mg/kg s.c.), and haloperidol (0.02 mg/kg s.c.) to produce a discriminative stimulus complex (DSC) is evidenced. The method is found to yield clear-cut data that are specifically related to drug discrimination learning without being possibly confounded by state dependent effects. In addition, the experimental procedure is designed so as to provide an appropriate measurement of operant response modulating drug effects.

Amphetamine↗
PubMed1976

Discriminative stimulus properties of benzodiazepines, barbiturates and pharmacologically related drugs; relation to some intrinsic and anticonvulsant effects.

Using a food-reinforced two-lever operant method, rats (n = 12) were trained to discriminate chlordiazepoxide (5 mg/kg, p.o.) from solvent (p.o.). With rats trained thus as subjects, generalization experiments were done with various benzodiazepines, barbiturates and related compounds, and with two neuroleptic drugs. The ability of these drugs to induce a discriminative stimulus complex similar to that induced by chlordiazepoxide, was then compared with some intrinsic and anticonvulsant effects of the same drugs. It was found that the discriminative stimulus properties of benzodiazepines, barbiturates, and related compounds correlate with the ability of these drugs to induce ataxia, as well as with part of their anticonvulsant activity. However, the stimulus properties of these drugs, as defined by the procedure described, are based neither on their ataxia-inducing effect, nor on their general depressant or sedative action. It is concluded that these properties constitute a pharmacologically highly specific phenomenon.

Animals↗
PubMed1976

Cocaine cue in rats as it relates to subjective drug effects: a preliminary report.

Using a food-reinforced two-lever operant method, rats (n=5) could be trained to discriminate 10 mg/kg cocaine from saline. Stimulus generalization experiments with lower doses (0.31-5.0 mg/kg) revealed that the cocaine cue is a dose-related phenomenon. Neuroleptic drugs were found relatively ineffective as possible antagonists of the cocaine cue, and no antagonistic effect whatsoever was obtained with dibenamine, propranolol, cyproheptadine and methysergide. iamphetamine (1.25 mg/kg) and apomorphine (0.31 mg/kg) were generalized with cocaine, and a dopaminergic involvement is discussed.

Amphetamine↗
PubMed1976

Discriminative stimulus properties of fentanyl and morphine: tolerance and dependence.

Using a food-reinforced two-lever operant procedure, rats were trained to discriminate 0.04 mg/kg fentanyl from saline. At different time intervals after the establishment of discriminative responding, stimulus generalization experiments were performed with equivalent dose ranges of fentanyl (0.0025 to 0.02 mg/kg) and morphine (2.5 to 20 mg/kg). It was found that the ED50 values of both compounds for generalization with the narcotic discriminative stimulus complex, did not change over a 4-month period. The subjects used in this study demonstrated marked tolerance to narcotic analgesia, but none of them showed signs reminescent of narcotic dependence. It is concluded that the discriminative stimulus properties of narcotic analgesics are not subject to tolerance.

Analgesics, Opioid↗
PubMed1976

Blockade of apomorphine's discriminative stimulus properties: relation to neuroleptic activity in neuropharmacological and biochemical assays.

Using a food-reinforced two-lever operant conditioning procedure, rats were trained to discriminate 0.16 mg/kg apomorphine from saline. Eight neuroleptics of the phenothiazine, butyrophenone or diphenylbutylamine type were investigated for thsir ability to antagonize the discriminative stimulus properties of apomorphine. The same drugs were also assayed for in vivo antagonism of apomorphine-induced stereotyped behavior as well as for in vitro inhibition of stereospecific 3-H-haloperidol binding in rat striatal tissue preparations. The data are consistent with the hypothesis that apomorphine exerts its discriminative stimulus properties by a mechanism similar to that underlying its stereotypogenic action. The loci involved in these two phenomena are likely to be distinct.

Animals↗
PubMed1976

The narcotic discriminative stimulus complex: relation to analgesic activity.

The ability of drugs to produce the narcotic discriminative stimulus complex is found to be highly correlated with their analgesic activity; in contrast, no relation with their antidiarrhoeal activity is evident. The findings suggest that the narcotic discriminative stimulus complex is a centrally mediated effect of narcotic drugs.

Analgesics, Opioid↗
PubMed1976

On the ability of narcotic antagonists to produce the narcotic cue.

The ability of narcotic antagonists to produce the narcotic cue was investigated in rats trained to discriminate fentanyl (0.04 mg/kg) from solvent. The partial antagonists pentazocine, cyclazocine and nalorphine were found to possess narcotic cuing activity whereas naloxone lacked any such action at doses up to 160 mg/kg. The relationship between the present findings and the ability of these drugs to produce opiate-like subjective effects in humans is discussed. The conclusion was reached that the experimental procedure used may contribute significantly to the preclinical evaluation of drug abuse liability.

Analgesics, Opioid↗
PubMed1976

Discriminative stimulus properties of analgesic drugs: narcotic versus non-narcotic analgesics.

Using a food-reinforced two-lever operant procedure, rats (n=6) were trained to discriminate fentanyl (1.25 mg/kg, p.o., t-60') from solvent (1 ml/100 g B.W., p.o., t-60'). The administration of another narcotic analgesic (pethidine) produced a dose-related generalization with the standard fentanyl treatment; six non-narcotic analygesics (suprofen, acetylsalicylic acid, indomethacin, phenacetin, phenylbutazone, tolmetin) were found not to do so. It is concluded that the ability of drugs to produce analgesia is not a sufficient condition for the drugs to produce the narcotic cue as well.

Analgesics↗
PubMed1976

Discriminative stimulus properties of a low dl-amphetamine dose.

Using a two-lever food-reinforced operant procedure, rats (n = 10) were trained to discriminate 0.16 mg/kg dl-amphetamine from saline. Over the dose range 0.08 to 0.63 mg/kg, cue detection was found to be dose-dependent (ED50: 0.13 mg/kg). However, 5 mg/kg dl-amphetamine was not generalized with the standard treatment. Further generalization experiments indicated that hydroxyamphetamine (ED50: 0.16 mg/kg) produces a discriminative stimulus similar to that of 0.16 mg/kg dl-amphetamine. Apomorphine (0.16 mg/kg), chlordiazepoxide (10 mg/kg), desipramine (10 mg/kg), fentanyl (0.04 mg/kg), haloperidol (0.04 mg/kg) and isopropamide (0.04 mg/kg) were not generalized with dl-amphetamine. Haloperidol (0.04 to 0.16 mg/kg) blocked the perception of 0.16 mg/kg dl-amphetamine in a dose-related way (ED50: 0.092 mg/kg). It is concluded that the discriminative stimulus properties of low dl-amphetamine doses differ qualitatively from those of high doses. The discriminative stimulus produced by 0.16 mg/kg dl-amphetamine presumably originates peripherally, whereas that produced by high doses of the drug reportedly is of central origin.

Amphetamine↗