Discriminative Stimulus Properties of Anxiolytic and Sedative Drugs: Pharmacological Specificity

Sanger, D. J.

doi:10.1007/978-3-642-73223-2_6

Cited by 13 publications

(14 citation statements)

References 35 publications

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“…Both compounds gave rise to a chlordiazepoxide-like discriminative cue and at a dose of 10 mg/kg substituted 100% for the training dose of chlordiazepoxide. However, the dose-response curves produced by Ro 16-6028 and Ro 17-1812 were flatter than those seen with most benzodiazepines and other compounds tested under similar conditions (Sanger et al 1985;Sanger 1987) with Ro 16-6028 giving rise to a dose-response curve less steep than that produced by Ro 17-1812. Cooper (1987) recently described a similar difference between the doseresponse curves produced by these two compounds in increasing intake of hypertonic saline in rats.…”

Section: Discussionmentioning

confidence: 76%

“…It has previously been argued (Sanger andZivkovic 1986, 1987;Sanger 1987) that the zolpidem cue is related to the ability of this compound to reduce rates of responding and to its selective sedative actions (Depoortere et al 1986). As neither Ro 16-6028 nor Ro 17-1812 exert sedative effects in rats in the range of dose used here and in other behavioural studies, the present results are consistent with this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…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). Similar, though not identical, results have been obtained with the/~-carboline mixed agonist/antagonist ZK 91296 (Stephens et al 1984;.…”

mentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Sanger

1987

Psychopharmacology

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“…In these studies the GABA A agonists did not fully substitute for the benzodiazepine discriminative stimulus, producing no greater than 45% druglever responding. In addition, progabide, a GABA prodrug, and its primary metabolite, SL 75102, failed to substitute for chlordiazepoxide in rodents (Sanger 1988). …”

Section: Drug Discrimination Procedures In Animals Have Been Used To mentioning

confidence: 97%

“…Balster thought to act by enhancement of GABAergic neurotransmission in the central nervous system (Sanger 1988;Young 1991). Most studies have focused on examining the indirect GABAA agonists such as the barbiturates and benzodiazepines.…”

Section: Drug Discrimination Procedures In Animals Have Been Used To mentioning

confidence: 99%

Pentobarbital-like discriminative stimulus effects of direct GABA agonists in rats

Grech

Balster

1993

Psychopharmacology

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The discriminative stimulus effects of direct and indirect-acting GABAergic drugs were investigated in rats trained to discriminate 5 mg/kg pentobarbital (PB) from saline under a two-lever fixed ratio (FR) 32 schedule of food reinforcement. PB and diazepam produced dose-dependent substitution for the training dose of PB with response rate reduction only at doses above those producing full substitution. Muscimol, thiomuscimol and 4,5,6,7-tetrahydroisoxazolo [5,4-c]-pyridin-3-ol (THIP) produced intermediate levels of pentobarbital-lever responding (40-60%), accompanied by dose-dependent decreases in rates of responding following THIP and muscimol administration. The GABAA agonist progabide and its metabolite 4-([(4-chlorophenyl) (5-fluoro-2-hydroxyphenyl)methylene]amino)] butyric acid (SL 75102) also partially substituted for PB, producing means of 39-73% PB-lever responding. The GABAB agonist, baclofen, completely failed to substitute for PB even at doses that decreased rates of responding. These results show that the discriminative stimulus effects of indirect GABAA agonists, PB and diazepam, although similar to one another, differ from those of direct GABAA receptor agonists, which produced only partial substitution for PB. The GABAB agonist, baclofen, can be distinguished by lacking any ability to substitute for PB. These results contribute to a further understanding of the similarities and differences in the behavioral effects of different types of GABA agonists.

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Drug discrimination by humans compared to nonhumans: current status and future directions

et al. 1993

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In drug discrimination (DD) procedures, behavior is differentially reinforced depending on the presence or absence of specific drug stimuli. The DD paradigm has been widely adopted by behavioral pharmacologists because of its specificity of stimulus control, concordance with drug action at cellular levels and its use as a preclinical model of subject-rated effects in humans. With the successful extension of DD to humans, a comparison of human and nonhuman DD will help place each in the context of the other. Twenty-eight studies of DD in humans are reviewed, including studies of amphetamine, opioid, benzodiazepine, caffeine, nicotine, marijuana and ethanol discriminative stimuli. Comparison of procedures between studies in humans and nonhumans reveals a common tradition, except the use of instructions appears to facilitate greatly DD acquisition in humans. Findings were qualitatively similar between humans and nonhumans. Potency relationships were quantitatively similar between humans and most, but not all, other species. Areas of human DD needing additional empirical evaluation include the influence of instructions, the effects of training dose and the effects of antagonists. Additionally, antihistamines, barbiturates, nicotine and marijuana are under-represented in human DD.

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Discriminative Stimulus Properties of Anxiolytic and Sedative Drugs: Pharmacological Specificity

Cited by 13 publications

References 35 publications

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

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

Pentobarbital-like discriminative stimulus effects of direct GABA agonists in rats

Drug discrimination by humans compared to nonhumans: current status and future directions

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