Discriminative-stimulus effects of azaspirodecanedione anxiolytics in baboons trained to discriminate β-carboline-3-carboxylic acid ethyl ester or pentylenetetrazole

Ator, Nancy A.; Cook, J. M.; Allen, Michael S.; Griffiths, R. R.

doi:10.1097/00008877-199404000-00009

Cited by 5 publications

(3 citation statements)

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“…Indeed, CL 218,872 was one of the first ligands identified as selective for BZ 1 receptors, and may be selective for benzodiazepine receptor subtypes in addition to BZ 1 sites (see Lüddens et al 1995, for review). As mentioned, the pK B values for flumazenil antagonism of the discriminative stimulus effects of β-CCE in baboons (Ator et al 1994) were lower than those of lorazepam, CL 218,872 and zopiclone in baboons. The lower pK B values suggest a site of action for β-CCE different from the other ligands tested in baboons.…”

Section: Apparent Pa 2 Analysismentioning

confidence: 76%

“…Flumazenil has been shown to competitively antagonize the discriminative stimulus effects of such benzodiazepines and benzodiazepine-related compounds as diazepam (Herling and Shannon 1982), chlordiazepoxide (Gauvin et al 1994), lorazepam Griffiths 1983, 1986), midazolam (Spealman 1985;Stolerman et al 1986;Woudenberg and Slangen 1989;Sannerud et al 1991;Sannerud and Ator 1995a) and β-carboline-3-carboxylic acid ethyl ester (β-CCE, Takada et al 1987;Ator et al 1994). In contrast, flumazenil has not been found to antagonize the discriminative stimulus effects of pentobarbital (Herling and Shannon 1982;Ator and Griffiths 1983;Willetts and Balster 1989;Woolverton and Nader 1995).…”

Section: Introductionmentioning

confidence: 99%

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Assessment of benzodiazepine receptor heterogeneity in vivo: apparent pA 2 and pK B analyses from behavioral studies

Rowlett

Woolverton

1996

Psychopharmacology

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The purpose of this review was to establish in vivo apparent pA2 and pKB values for antagonism of the discriminative stimulus effects of benzodiazepine ligands, and to compare these values to those obtained from other behavioral procedures. Articles were chosen from the Medline data base from January 1976 to August 1995. This literature consisted of studies with flumazenil (Ro 15-1788) as the antagonist, as well as other benzodiazepine ligands (beta-carbolines, CGS 9896, CGS 8216). The dose which occasioned 50% of the maximal response (ED50) was obtained from values estimated from the graphs presented in each article. These ED50 values were used to conduct apparent pKB and apparent pA2 analyses. Apparent pA2 values for antagonism of the discriminative stimulus effects of diazepam in rats were the following (antagonist, pA2, slope): flumazenil, 4.7, -1.5; beta-CCE, 4.0, -3.0; beta-CCtB, 5.0, -2.2. The apparent pA2 value for CGS 8216 antagonism of the discriminative stimulus effects of diazepam in rats was 5.74, -2.22 (reported in Shannon and Davis 1984). The mean apparent pA2 value for flumazenil antagonism of the discriminative stimulus effects of diazepam in rhesus monkeys was 6.55, with a mean slope of -1.42. Analysis of baboon data from Ator and Griffiths (1986) revealed apparent pKB values for flumazenil antagonism of the discriminative stimulus effects of lorazepam that were lower than the pKB values for either zopiclone or CL 218,872. Analyses of the pKB data also revealed the following: no effect of route of administration (rat, PO versus IP; baboon, PO versus IM), no effect of pretreatment time (grouped into two categories: 10-20 min and 40-70 min, in rats and non-human primates), and a species effect (pKB values for rats were reliably lower than either non-human primates or pigeons, rhesus monkeys were lower than baboons). The apparent pA2 and pKB values obtained in the present review were similar across behavioral assays, except that, in squirrel monkeys, flumazenil pKB values for antagonism of benzodiazepine-induced decreases in schedule-controlled behavior were lower than pKB values obtained from drug discrimination studies. This review provides apparent pA2 values for antagonism of the discriminative stimulus effects of benzodiazepine ligands and provides evidence from pKB analyses consistent with functional heterogeneity of benzodiazepine receptors in vivo.

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Section: Apparent Pa 2 Analysismentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Assessment of benzodiazepine receptor heterogeneity in vivo: apparent pA 2 and pK B analyses from behavioral studies

Rowlett

Woolverton

1996

Psychopharmacology

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“…Buspirone does not alter the discriminative stimulus effects of either PTZ [Ator et al, 1994] or mCPP [Callahan and Cunningham, 1994], and when given during EW does not block spontaneous PTZ-lever pressing (Fig. 2).…”

Section: Monoaminergic Sites Serotonergic Receptorsmentioning

confidence: 88%

Animal models of the anxiogenic effects of ethanol withdrawal

Gatch¹,

Lal²

2001

Drug Development Research

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Although anxiety is a major feature of ethanol withdrawal (EW) and much of treatment related to EW is focused on amelioration of the anxiety experienced during EW, less attention has been given to the anxiogenic effects of EW than to the convulsant effects. In this article, we review the animal literature on the anxiogenic effects of EW. Both GABA A and serotonin (5-HT) receptors are important targets in the treatment of anxiety. The roles of each of these two receptors on the anxiogenic effects of EW as well as their potential interrelation are discussed. The contribution of other receptor systems to the modulation of these effects is reviewed. Additionally, males and females show very different levels of anxiety during EW and studies on the role of the HPA axis in mediating these effects are examined. Finally, potential directions for better treatments for EW are discussed. Drug Dev. Res. 54:95-115, 2001.

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Discriminative stimulus effects of ethyl-β-carboline-3-carboxylate at two training doses in rats

Rowlett¹,

Wilcox²,

Woolverton³

1999

Psychopharmacology

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Discriminative-stimulus effects of azaspirodecanedione anxiolytics in baboons trained to discriminate β-carboline-3-carboxylic acid ethyl ester or pentylenetetrazole

Cited by 5 publications

References 0 publications

Assessment of benzodiazepine receptor heterogeneity in vivo: apparent pA 2 and pK B analyses from behavioral studies

Assessment of benzodiazepine receptor heterogeneity in vivo: apparent pA 2 and pK B analyses from behavioral studies

Animal models of the anxiogenic effects of ethanol withdrawal

Discriminative stimulus effects of ethyl-β-carboline-3-carboxylate at two training doses in rats

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