The non-sedating anxiolytic CGS 9896 produces discriminative stimuli that may be related to an anxioselective effect

Bennett, Debra A.

doi:10.1016/0024-3205(85)90539-9

Cited by 33 publications

(8 citation statements)

References 14 publications

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“…Some of the newer nonbenzodiazepines that bind the benzodiazepine receptor may stand in the same relation to benzodiazepines as ethanol does to barbiturates and benzodiazepines. For example, CGS 9896-trained rats showed generalization to diazepam (Bennett 1985) but CGS 9896 has not always occasioned drug lever responding in benzodiazepine-trained animals Sanger et al 1985;Ator and Griffiths 1986).…”

Section: Discussionmentioning

confidence: 94%

Differential generalization to pentobarbital in rats trained to discriminate lorazepam, chlordiazepoxide, diazepam, or triazolam

Ator

Griffiths

1989

Psychopharmacology

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In drug discrimination studies benzodiazepine-trained animals have typically responded on the drug lever when tested with barbiturates. In a recent study, greater specificity appeared to be shown when lorazepam was used as a training drug. The generality and limits of this finding were explored in the present set of experiments. The asymmetrical cross-generalization found in lorazepam- and pentobarbital-trained baboons was replicated in rats and was shown not to be a function of either lorazepam (0.1., 0.32, or 1.0 mg/kg) or pentobarbital (10 or 25 mg/kg) training dose (i.e., pentobarbital-trained rats responded on the drug lever in tests with lorazepam, but lorazepam-trained rats did not show comparable pentobarbital generalization). In the next experiment, groups of rats were trained to discriminate chlordiazepoxide (10 mg/kg), triazolam (0.1 mg/kg), or diazepam (1.0 mg/kg). Generalization to both lorazepam and pentobarbital was shown by these rats. Finally after daily pentobarbital administration, lorazepam-trained rats made a sufficient number of responses after high pentobarbital doses to permit extension of the range of pentobarbital doses tested. Pentobarbital generalization increased, but still did not occur in all rats and was unreliable in successive tests in the same rats. These results suggest less homogeneity in the discriminative stimulus effects of "depressant drugs" than generally has been recognized.

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Section: Discussionmentioning

confidence: 94%

Differential generalization to pentobarbital in rats trained to discriminate lorazepam, chlordiazepoxide, diazepam, or triazolam

Ator

Griffiths

1989

Psychopharmacology

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“…For example, the pyrazoloquinoline, CGS 9896 (Yokoyama et al 1982;Bennett and Petrack 1984) has benzodiazepine-like stimulus properties in rats trained to discriminate chlordiazepoxide (Sanger et al 1985; but is not generalised by rats trained to discriminate diazepam (Shannon and Herling 1983 b) or by rats or baboons trained with lorazepam (Ator and Griffiths 1986). Nevertheless, when rats were trained to discriminate CGS 9896 itself, drug-appropriate responding did occur after administration of diazepam and CL 218,872 as well as after meprobamate and tracazolate, which do not bind to benzodiazepine receptors (Bennett 1985). In addition, CGS 9896 did not antagonise the diazepam cue (Shannon and Herling 1983b) but produced a dose-related antagonism of the discriminative stimulus produced by zolpidem, a novel non-benzodiazepine ligand for benzodiazepine receptors (Depoortere et al 1986;Sanger andZivkovic 1986, 1987).…”

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confidence: 99%

Further investigation of the stimulus properties of chlordiazepoxide and zolpidem. Agonism and antagonism by two novel benzodiazepines

Sanger

1987

Psychopharmacology

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The effects of Ro 16-6028 and Ro 17-1812, two novel benzodiazepines with mixed agonist and antagonist properties, were studied in rats trained to discriminate either chlordiazepoxide or the benzodiazepine receptor ligand zolpidem. In rats discriminating 5 mg/kg chlordiazepoxide from saline both Ro 16-6028 and Ro 17-1812 produced responding on the drug lever. At a dose of 10 mg/kg both compounds gave rise to 100% responding on the lever associated with chlordiazepoxide. The dose-response curve produced by Ro 16-6028 was flatter than that for Ro 17-1812, however. The discriminative cue produced by 2 mg/kg zolpidem did not generalise to either Ro 16-6028 or Ro 17-1812. In contrast, both of those compounds antagonised the zolpidem cue and also antagonised the reduction in response rates produced by zolpidem. These results are consistent with previous findings that Ro 16-6028 and Ro 17-1812 may exert anxiolytic-like effects typical of benzodiazepines while antagonising the depressant actions of benzodiazepine receptor ligands. The results are also consistent with the suggestion that the discriminative cues produced by chlordiazepoxide and zolpidem may be mediated, at least partially, by activity at different sub-types of benzodiazepine receptors.

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“…Furthermore, novel benzodiazepine partial agonists (Ro16-6028, Ro17-1812, Ro23-0364) and putative 5-HTIA agonists (8-OH-DPAT, gepirone, ipsapirone) also strongly stimulate the ingestion of hypertonic saline [Coopcr, 1987;Cooper and Desa, 1987;Cooper ct al., 19881. Two pyrazoloquinolines stand as exceptions to the general rule that benzodiazepinereceptor agonists enhance the consumption of hypertonic NaCl solutions. CGS 9895 and CGS 9896 show high-affinity binding to benzodiaLepine receptors [Wood et al, 19841 and produce behavioral effects in animal models that are predictive of anxiolytic activity [Bennett, 1985;Bennett and Amrick, 1987;Bennett et al. 1985;Bennett and Petrack, 1984;Bernard et al, 1985;Sanger and July, 1985;Sangcr et al, 1985;Smith and Crawley, 1986;Spencer and Lal, 19831.…”

Section: Introductionmentioning

confidence: 98%

Pyrazoloquinolines and zolpidem: Effects on hypertonic saline consumption in rehydrating rats

Cooper

Desa

1988

Drug Development Research

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Cooper, S. J., and A. Desa: Pyrazoloquinolines and zolpidem: Effects on hypertonic saline consumption in rehydrating rats. Drug Dev. Res. 14:161-168, 1988.Male rats were adapted to a 22-hr-daily water-deprivation schedule and to consuming an aversive 2.7% NaCl solution in a 30-min period. Previous reports had shown that benzodiazepines and other anxiolytics stimulate ingestion of hypertonic saline under these conditions; however, two pyrazoloquinolines, CGS 9895 and CGS 9896, failed to do so [Cooper, 19871. The present experiments were designed to investigate possible antagonist properties of CGS 9895 and CGS 9896 in this model and also to characterize the effects of a newly described pyrazoloquinoline, CGS 17867A, on saline drinking. In addition, a novel sedative-hypnotic, zolpidem, and a benzodiazepine peripheral-type receptor compound, Ro5-4864, were treated. The results indicate that CGS 9895 and CGS 9896 exhibited antagonistic activity in this model, that CGS 17867A increased salt drinking without displaying antagonist activity, and that neither zolpidem nor Ro5-4864 affected drinking responses.

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The non-sedating anxiolytic CGS 9896 produces discriminative stimuli that may be related to an anxioselective effect

Cited by 33 publications

References 14 publications

Differential generalization to pentobarbital in rats trained to discriminate lorazepam, chlordiazepoxide, diazepam, or triazolam

Differential generalization to pentobarbital in rats trained to discriminate lorazepam, chlordiazepoxide, diazepam, or triazolam

Further investigation of the stimulus properties of chlordiazepoxide and zolpidem. Agonism and antagonism by two novel benzodiazepines

Pyrazoloquinolines and zolpidem: Effects on hypertonic saline consumption in rehydrating rats

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