Does the pentylenetetrazole (PTZ) cue reflect PTZ‐induced kindling or PTZ‐induced anxiogenesis?

Andrews, John S.; Turski, Lechosław; Stephens, David

doi:10.1002/ddr.430160218

Cited by 16 publications

(6 citation statements)

References 22 publications

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“…Emmett-Oglesby et al 1983). The PTZ cue may be related to its proconvulsant actions (Andrews et al 1989); thus absence of PTZ generalization suggests that the clozapine cue is not related to clozapines ability to induce seizures (Pacia and Devinsky 1994). The typical neuroleptics haloperidol and loxapine failed to generalise, in agreement with reports that various typical neuroleptics do not generalise to clozapine in rats (Goas and Boston 1978;Browne and Koe 1982;Ortmann et al 1986;Wiley and Porter 1992;Franklin and Tang 1994;Tang et al 1997), pigeons (Hoenicke et al 1992) and monkeys (Carey and Bergman 1997).…”

Section: Discussionmentioning

confidence: 99%

Comparative characterisation of the discriminative stimulus properties of clozapine and other antipsychotics in rats

Goudie¹,

Taylor²

1998

Psychopharmacology

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The discriminative stimulus properties of the prototypical atypical neuroleptic clozapine (5 mg/kg, IP) were characterised in rats using a fixed ratio assay. Clozapine induced full dose-related generalization in the absence of response suppression. Amphetamine and pentylenetetrazol failed to generalise at doses known to be discriminable, showing a degree of specificity for the clozapine cue. The typical neuroleptics haloperidol and loxapine induced minimal (20%) generalization at doses with marked behavioural effects; thus clozapine discrimination dissociates clozapine from typical neuroleptics. Atypical neuroleptics which are not clozapine congeners produced weak partial generalization when tested up to the highest doses that could be studied. The maximal levels of generalization induced by these agents were: amisulpiride 28%, risperidone 40% and sertindole 50%. Clozapine congeners typically caused more generalization, the novel pyridobenzoxapine JL13 inducing 70% maximal generalization. Most generalization (83%) was seen with the clozapine congener seroquel, although in contrast to clozapine, it only generalised at doses with marked effects on responding, so that no drug mimicked clozapine fully. Surprisingly, the clozapine congener olanzapine only induced a maximal level of 38% generalization. This apparently anomalous finding is attributed to an inability to test high doses of the drug due to its rate-suppressant actions. The clozapine cue can be used to rank atypical neuroleptics in terms of their similarity to clozapine in vivo. The clozapine cue is probably a compound cue, since only agents showing "polyvalent" receptor pharmacology induced substantial generalization.

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Section: Discussionmentioning

confidence: 99%

Comparative characterisation of the discriminative stimulus properties of clozapine and other antipsychotics in rats

Goudie¹,

Taylor²

1998

Psychopharmacology

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“…For this reason, the e¤ects of repeated administration of initially subconvulsant doses of the convulsant, PTZ, a procedure which leads to kindling of seizures to PTZ (e.g. Andrews et al 1989), was studied. As anticipated, the e¤ect of repeated subthreshold doses of PTZ produced a sensitised response to the convulsant e¤ects of an acute IV infusion of PTZ (reduced threshold); furthermore, the patterns of behavioural change following a single dose, and repeated doses of PTZ generally resembled those following a single, or repeated withdrawals, respectively, though in the PTZ-treated animals, the e¤ects did not always reach signiÞcance.…”

Section: Exptmentioning

confidence: 99%

“…This may reßect transient adaptive changes in the GABA and NMDA systems. Such data suggest that the transient hyperexcitability following ethanol administration could, upon repetition, kindle in a similar manner as repeated administration of PTZ (Ito et al 1977;Andrews et al 1989) and inverse agonist benzodiazepines (Little et al 1984;Stephens and Weidmann 1989), both of which, like ethanol, have the GABA A receptor chloride channel complex as their site of action. The question then arises whether repeated experience of withdrawal from benzodiazepines, which also act to facilitate transmission at GABAergic synapses, might also give rise to intensiÞcation of withdrawal signs.…”

Section: Introductionmentioning

confidence: 96%

Sensitisation of withdrawal signs following repeated withdrawal from a benzodiazepine: differences between measures of anxiety and seizure sensitivity

Ward

Stephens

1998

Psychopharmacology

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Three experiments examined the effect of either withdrawal from diazepam, or repeated treatment with the convulsant, pentylenetetrazol (PTZ), on behaviour and seizure threshold. The behaviours measured were on the elevated plus maze and in the four-plate test; seizure threshold was measured as dose of PTZ infused via the tail vein to the first clonic twitch. In experiment 1, we examined the effect of either single or repeated withdrawal from diazepam using a procedure in which the drug was administered SC in a slow release depot. Three cycles of withdrawal from diazepam were compared to a single withdrawal experience. A single withdrawal from diazepam following chronic treatment gave rise, 72 h following the last dosing, to behavioural changes, suggestive of anxiety, in both tests, but did not result in a reduced convulsant threshold. In contrast, repeated withdrawal resulted in a reduction in sensitivity in several measures of anxiety, but sensitised the mice to the convulsive effects of the PTZ. The unexpected failure to find an increased sensitivity to a convulsive agent following a single withdrawal from SC diazepam was examined in experiment 2. The seizure threshold following a single withdrawal of mice which had received diazepam chronically IP in aqueous vehicle was significantly reduced relative to vehicle-treated controls, whereas that of animals receiving the same dose SC in oil, was not. It is argued that the difference may arise from the animals treated repeatedly with IP diazepam unintentionally experiencing repeated withdrawal, since the half-life of the drug by this route is short. In experiment 3, repeated sub-convulsant PTZ treatment reduced the convulsant threshold (the dose of PTZ required to give rise to the first clonic twitch), but had no significant effect on the behavioural measures of anxiety compared to a single dose of PTZ or vehicle controls. The results suggest that repeated withdrawal from chronic treatments with diazepam sensitises mice to convulsant stimuli in a manner resembling the effects of repeated administration of sub-convulsant doses of PTZ, but that neither repeated PTZ nor repeated diazepam withdrawal results in increased sensitivity to anxiogenic stimuli; rather, repeated withdrawal from diazepam may reduce the susceptibility of mice to behavioural measures of anxiety.

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“…In tests of its discriminative stimulus effects in animals, La1 and colleagues [Shearman and Lal, 1980;La1 and Emmett-Oglesby, 1983;La1 and Fielding, 19841 have argued that PTZ is useful for assessing anxiogenic and anxiolytic drugs. Recently, however, Andrews et al [1989] have argued that the potency of drugs that block the PTZ cue is better correlated with their anticonvulsant rather than their anxiolytic effects. This conclusion has been challenged [Emmett-Oglesby et al, 1987, 19901, and the present data also suggest that the convulsant activity produced by PTZ is independent of its stimulus properties.…”

Section: -mentioning

confidence: 99%

Assessment of zolpidem and Cl‐966 for anxiolytic and anxiogenic properties by using the discrimination of pentylenetetrazole by rats

Emmett‐Oglesby

Abdel-Malek

1990

Drug Development Research

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Emmett-Oglesby, M.W., and S.L. Abdel-Malek: Assessment of zolpidem and Cl-966 for anxiolytic and anxiogenic properties by using the discrimination of pentylenetetrazole by rats. Drug Dev. Res. 21 :243-252, 1990. This experiment determined if two novel compounds, zolpidem and Cl-966, would show anxiogenic or anxiolytic activity in an animal model of anxiety based upon the discrimination of pentylentetrazole (PTZ). Rats were trained to detect the anxiogenic drug PTZ, 20 mgikg, and tested with zolpidem (an agonist at omega [benzodiazepine] receptors) and Cl-966 (a GABA-uptake inhibitor). Zolpidem did not substitute for PTZ. This drug blocked the PTZ stimulus in a dose-related manner (0.32-5.0 mg/kg), although only partial blockade was obtained even at the highest dose that could be tested. These data suggest that zolpidem may have weak efficacy as an anxiolytic drug. Cl-966 partially substituted for PTZ at 3 to 6 hr post injection of doses of 16.0 and 32.0 mg/kg. Lower doses of Cl-966 produced a slight, but non-significant, blockade of the PTZ stimulus, which appeared to be additive with the blocking effects of diazepam upon this discrimination. Because (3-966 has been shown to block PTZ seizures in mice, the present data suggest that the discriminative stimulus produced by PTZ is not related to its ability to produce convulsions. The partial substitution of (3-966 given in high doses is consistent with clinical reports that this compound may produce anxiogenic effects.

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Does the pentylenetetrazole (PTZ) cue reflect PTZ‐induced kindling or PTZ‐induced anxiogenesis?

Cited by 16 publications

References 22 publications

Comparative characterisation of the discriminative stimulus properties of clozapine and other antipsychotics in rats

Comparative characterisation of the discriminative stimulus properties of clozapine and other antipsychotics in rats

Sensitisation of withdrawal signs following repeated withdrawal from a benzodiazepine: differences between measures of anxiety and seizure sensitivity

Assessment of zolpidem and Cl‐966 for anxiolytic and anxiogenic properties by using the discrimination of pentylenetetrazole by rats

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