Differential effects of clozapine and pimozide on fixed-ratio responding during repeated dosing

Wiley, Jenny L.; Compton, Amelia D.; Porter, Joseph H.

doi:10.1016/0091-3057(94)90524-x

Cited by 15 publications

(21 citation statements)

References 25 publications

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“…In the present study, CLOZ-induced sedation and suppression of lever pressing showed signs of tolerance within the 14-day test period. Other work with rats has also indicated that the suppression of lever pressing induced by CLOZ can show tolerance (Kaempf and Porter 1987;Wiley et al 1994). The neural mechanisms mediating CLOZ-induced sedation, and tolerance to this effect, are not well understood, although alpha-adrenergic and histamine systems have been implicated (Safferman et al 1991).…”

Section: Fig $ Effects Of Repeated Daily Vehicle (Solid Line) or Drumentioning

confidence: 94%

“…Previous work indicated that CLOZ suppressed lever pressing with acute injections, but this effect showed tolerance (Wiley et al 1994). The present study also evaluated the DA antagonist thioridazine (THIO), because this drug is thought to be intermediate between haloperidol and CLOZ in terms of the production of extrapyramidal motor effects.…”

Section: Introductionmentioning

confidence: 95%

“…CmTently, there is considerable interest in characterizing the differences between the behavioral effects of CLOZ and the more typical antipsychotic drugs (Koek and Colpaert 1993;Mueller 1993;Wiley et al 1994). Antipsychotic drugs generally act to antagonize dopamine (DA) receptors, and one of the most widely studied effects of DA antagonists is the suppression of lever pressing (Rolls et al 1974;FiNger et al 1976;Wise et al 1978a,b;Wise 1982;Salamone 1986Salamone , 1991Salamone , 1992.…”

Section: Introductionmentioning

confidence: 98%

“…Antipsychotic drugs generally act to antagonize dopamine (DA) receptors, and one of the most widely studied effects of DA antagonists is the suppression of lever pressing (Rolls et al 1974;FiNger et al 1976;Wise et al 1978a,b;Wise 1982;Salamone 1986Salamone , 1991Salamone , 1992. DA antagonists with very diverse profiles, including nonselective, D 1 or D 2 selective, or atypical antagonists, all act to suppress lever pressing (Beninger et al 1987;Wiley et al 1994).…”

Section: Introductionmentioning

confidence: 99%

“…However, the effects of CLOZ have not been evaluated using this lever pressing/feeding procedure. It has been suggested that instrumental behavior methods could be useful for identifying differences between the behavioral effects of CLOZ and typical antipsychotic drugs (Wiley et al 1994). Therefore, in the present study the effects of haloperidol and CLOZ were assessed using the instrumental lever pressing/feeding procedure.…”

Section: Introductionmentioning

confidence: 99%

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Different behavioral effects of haloperidol, clozapine and thioridazine in a concurrent lever pressing and feeding procedure

et al. 1996

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Rats were tested using a lever pressing/feeding procedure in which a preferred food (Bioserve pellets) was available by pressing a lever on a fixed ratio 5 schedule, but a less preferred food (lab chow) was also available concurrently in the operant chamber. The effects of repeated (14 day) injections of haloperidol, clozapine and thioridazine were compared. Haloperidol (0.05-0.15 mg/kg) significantly reduced lever pressing and increased chow intake throughout the drug treatment period. Injections of clozapine (2.0-6.0 mg/kg) suppressed lever pressing but failed to produce substantial increases in chow intake. In the haloperidol experiment there was a significant inverse correlation between lever pressing and chow intake, but in the clozapine experiment there was not. Regression analysis indicated that rats treated with the high dose of clozapine showed some tolerance to the suppression of lever pressing. Tests of sedation also were conducted before and after the instrumental behavior sessions. Haloperidol produced little or no sedative effect in the dose range tested. Clozapine produced substantial sedation during the first 10 days of administration, but this effect, like the suppression of lever pressing, showed signs of tolerance. Thioridazine (3.0-9.0 mg/kg) produced some effects that resembled haloperidol, and other effects, including sedation, that resembled clozapine. These studies indicate that haloperidol suppresses lever pressing for food at low doses that do not produce severe motivational or sedative effects that disrupt food intake. In contrast, it appears as though the suppression of lever pressing produced by clozapine stems from a sedative effect that also serves to set limits on chow intake. These results indicate that haloperidol and clozapine suppress lever pressing through different mechanisms.

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Section: Fig $ Effects Of Repeated Daily Vehicle (Solid Line) or Drumentioning

confidence: 94%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Different behavioral effects of haloperidol, clozapine and thioridazine in a concurrent lever pressing and feeding procedure

et al. 1996

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Effects of antipsychotic drugs on operant responding after acute and repeated administration

Varvel

et al. 2002

Psychopharmacology

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Quetiapine (Seroquel) shows a pattern of behavioral effects similar to the atypical antipsychotics clozapine and olanzapine: studies with tremulous jaw movements in rats

et al. 2004

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Rationale: Previous studies demonstrated that clozapine and olanzapine suppressed tacrine-induced jaw movements at lower doses than those required for suppression of lever pressing. Objective: The present studies were undertaken to evaluate the novel atypical antipsychotic quetiapine using the jaw movement model. Methods: The effect of acute quetiapine on the suppression of tacrineinduced tremulous jaw movements was examined. To determine the relative potency of this effect compared with other behavioral effects of quetiapine, suppression of lever pressing also was studied. In other studies, rats received quetiapine for 14 consecutive days to study the effects of repeated injections of this drug. Results: Acute quetiapine injections decreased tacrine-induced jaw movements and lever pressing. The ratio of the ED 50 for suppression of jaw movements divided by the ED 50 for suppression of lever pressing was used as an index of liability to produce motor side effects, and the present results demonstrate that quetiapine has a ratio similar to that previously shown for clozapine and olanzapine. In the repeated-administration studies, quetiapine failed to induce jaw movements. On day 14, quetiapine reduced tacrine-induced tremulous jaw movements, and in a parallel experiment quetiapine significantly suppressed lever pressing on days 1-14. Repeated injections of quetiapine reduced tacrine-induced jaw movements over a dose range lower than that required for suppression of lever pressing. Conclusions: On tests of jaw movement activity and lever pressing after both acute and repeated drug administration, quetiapine showed a profile somewhat similar to clozapine and olanzapine. A theoretical model is offered suggesting that atypical antipsychotics that act on 5-HT or muscarinic receptors have intrinsic antiparkinsonian actions that work in opposition to the motor effects produced by dopamine antagonism.

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Differential effects of clozapine and pimozide on fixed-ratio responding during repeated dosing

Cited by 15 publications

References 25 publications

Different behavioral effects of haloperidol, clozapine and thioridazine in a concurrent lever pressing and feeding procedure

Different behavioral effects of haloperidol, clozapine and thioridazine in a concurrent lever pressing and feeding procedure

Effects of antipsychotic drugs on operant responding after acute and repeated administration

Quetiapine (Seroquel) shows a pattern of behavioral effects similar to the atypical antipsychotics clozapine and olanzapine: studies with tremulous jaw movements in rats

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