The pentylenetetrazole-cue antagonist actions of bretazenil (Ro 16-6028) as compared to midazolam

Rijnders, Henk J.; Järbe, Torbjörn U. C.; Slangen, Jef L.

doi:10.1016/0091-3057(91)90409-u

Cited by 11 publications

(7 citation statements)

References 15 publications

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“…Haloperidol, R 79598 and sulpiride each showed a partial generalization to buspirone (between 50 and 76% buspirone appropriate responding). For haloperidol, our findings confirm data reported by Ator (1991) and by Rijnders and Slangen (1991). Tile partial generalization of haloperidot attained the highest percentage of buspirone responding in the present study (76%).…”

Section: Discussionsupporting

confidence: 92%

“…The complete substitution by 8-OH-DPAT is consistent with previous reports for rats (Ator 1991;Rijnders and Slangen 1991), as well as for pigeons (Mansbach and Barrett 1987;Nader et al 1989). It indicates that a 5-HT~, receptor activation mediates the discriminative stimulus properties of buspirone in rats.…”

Section: Discussionsupporting

confidence: 91%

“…It appears therefore that haloperidol gives rise to a higher percentage of buspirone responding when the training dose of buspirone is higher, and that the dopaminergic involvement in 59 extrapolation the buspirone cue becomes more pronounced at higher doses. Note, however, that in the study of Rijnders and Slangen (1991), and in the present study, relatively high doses of haloperidol, up to 1.0mg/kg could be tested, whereas Ator (1991) reported a dramatic response rate decrement at 0.32 mg/kg haloperidol and abandoned testing at higher doses. Repeated administration of relatively high doses of buspirone seems to make animals less sensitive to the response disruptive effects of haloperidol.…”

Section: Discussioncontrasting

confidence: 55%

“…The buspirone training dose may play an important role. Rijnders and Slangen (1991) reported a maximum percentage of buspirone responding of 55% after haloperidot administration in rats trained to discriminate 2.0 mg/kg buspirone from saline, whereas Ator (1991) found maximum mean scores of 40% for the low training dose group (0.56 mg/kg buspirone versus saline), and 60% for the high training dose group (1.0 mg/kg buspirone versus saline). It appears therefore that haloperidol gives rise to a higher percentage of buspirone responding when the training dose of buspirone is higher, and that the dopaminergic involvement in 59 extrapolation the buspirone cue becomes more pronounced at higher doses.…”

Section: Discussionmentioning

confidence: 99%

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The discriminative stimulus properties of buspirone involve dopamine-2 receptor antagonist activity

Rijnders

Slangen

1993

Psychopharmacology

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To investigate a dopaminergic component in the discriminative stimulus properties of buspirone, rats were trained to discriminate 2.5 mg/kg buspirone from saline, using a two lever, food-rewarded, fixed ratio 10 operant procedure. To test the dopamine-2 (D2) antagonist action of buspirone, a second group of rats was trained to discriminate 0.16 mg/kg apomorphine from saline. In addition to a complete generalization to 8-OH-DPAT, the D2 antagonists haloperidol, R 79598 and sulpiride showed a partial generalization to buspirone. The benzodiazepine ligands chlordiazepoxide and bretazenil did not generalize to the buspirone cue. Buspirone (2.0 mg/kg) completely blocked the apomorphine cue in the apomorphine trained rats. Haloperidol, R 79895 and sulpiride also blocked the apomorphine cue, although at doses much smaller than the doses needed to evoke buspirone responding in the buspirone trained group. 8-OH-DPAT did not antagonize apomorphine. It was concluded that the D2 action of buspirone partially contributes to its discriminative stimulus properties. Mediation of the buspirone cue by 5-HT1a receptor activation seemed predominant. Further, buspirone can act as a full D2 antagonist in drug discrimination. A model was proposed suggesting a compound discriminative stimulus complex of buspirone with a dominant 5-HT1a component that overshadows a less pronounced D2 component.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

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The discriminative stimulus properties of buspirone involve dopamine-2 receptor antagonist activity

Rijnders

Slangen

1993

Psychopharmacology

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“…The present results with alprazolam are comparable with training of the high dose of CDP. Rijnders et al (1991) Midazolam PTZ 29 Haug (1983) Diazepam PTZ 0 McElroy and Feldman (1982) CDP-CL 218,872 b PTZ <20 Leidenheimer and Schechter (1988) CGS 9896 PTZ 0 Woudenberg and Slangen (1989) CDP PTZ 0 Woudenberg and Slangen (1989) CDP PTZ 100 Present study Alprazolam Picrotoxin 75 Stolerman et al (1986) Midazolam c Picrotoxin 14 Stolerman et al (1986) Midazolam Picrotoxin 100 Shannon et al (1988) Diazepam Picrotoxin 75 Kalinina et al (1994) Phenazepam Picrotoxin No antagonism d Kalinina et al (1994) Gidazepam Pentylenetetrazole (PTZ) was able partially to antagonize the alprazolam stimulus. The mechanism of PTZ is not entirely clear but PTZ is thought to have a specific binding site at the GABA A receptor (Johnston 1996), blocking GABA mediated chloride-ion influx.…”

Section: Discussionmentioning

confidence: 93%

Discriminative stimulus properties of alprazolam

et al. 2000

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Evaluation of the discriminative stimulus effects of the novel sedative-hypnotic CL 284,846

Vanover¹,

Barrett²

1994

Psychopharmacology

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CL 284,846, N-[3-(3-cyanopyrazolo[1, 5-a]pyrimidin-7-yl)phenyl)]-N- ethylacetamide, is a novel non-benzodiazepine sedative-hypnotic with benzodiazepine-like sedative effects, but with less apparent liability for accompanying undesired side effects. In an effort to further characterize its pharmacological activity, CL 284,846 (3.0 mg/kg, IP, 30 min pretreatment) was established as a discriminative stimulus (DS) in rats (n = 7). CL 284,846 (0.3-10.0 mg/kg) showed a dose-related increase in drug-appropriate responding up to the training dose and a dose-related decrease in response rate. The benzodiazepine agonist triazolam (0.1-1.0 mg/kg), the benzodiazepine partial agonist Ro 17-1812 (0.3-3.0 mg/kg) and the triazolopyridazine CL 218,872 (1.0-3.0 mg/kg) substituted for CL 284,846 in all rats, whereas the imidazopyridines zolpidem (3.0-10.0 mg/kg) and alpidem (10.0-30.0 mg/kg), the benzodiazepine partial agonist bretazenil (0.03-10.0 mg/kg) and the novel putative anxiolytic CL 273,547 (10.0-56.0 mg/kg) substituted in most, but not all, rats. Ro 17-1812, bretazenil, and CL 218,872 had no effect on response rate while the other drugs showed a concomitant decrease in rate. The 5-HT1A agonist buspirone (1.0-10.0 mg/kg) and the barbiturate pentobarbital (3.0-17.0 mg/kg) failed to substitute for CL 284,846 up to rate-decreasing doses. The benzodiazepine antagonist flumazenil (3.0-10.0 mg/kg) blocked the DS effects of CL 284,846 in most rats with no effect on response rate. Taken together, these results suggest that the DS effects of CL 284,846 are mediated via benzodiazepine receptors; however, the DS profile of CL 284,846 remains distinct from both benzodiazepine and non-benzodiazepine sedative-hypnotic drugs.

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The pentylenetetrazole-cue antagonist actions of bretazenil (Ro 16-6028) as compared to midazolam

Cited by 11 publications

References 15 publications

The discriminative stimulus properties of buspirone involve dopamine-2 receptor antagonist activity

The discriminative stimulus properties of buspirone involve dopamine-2 receptor antagonist activity

Discriminative stimulus properties of alprazolam

Evaluation of the discriminative stimulus effects of the novel sedative-hypnotic CL 284,846

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