Typical and atypical neuroleptics antagonize MK-801-induced locomotion and stereotypy in rats

Dc, Hoffman

doi:10.1007/bf01245347

Cited by 114 publications

(47 citation statements)

References 32 publications

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“…The observation that dizocilpine significantly decreased running times in the maze is also in line with studies showing a dizocilpine-induced increase of spontaneous locomotor activity (Tiedtke et al, 1990;Hoffman, 1992). Regarding the relationship between errors and corresponding running times, both measures seem to be independent regardless of the treatment used here: I) Dizocilpine-treated animals had the same running times in correct and incorrect choices.…”

Section: Discussionsupporting

confidence: 70%

“…Recent studies showed that clozapine antagonized dizocilpine-induced stereotypy (Tiedtke etal., 1990;Hoffman, 1992). Furthermore, stereotypy induced by intrastriatal injection of AP-5 was antagonized by systemic administration of clozapine (Schmidt, 1986).…”

Section: Introductionmentioning

confidence: 85%

“…In rodents NMDA antagonists induce a strong behavioural activation characterized by an increased locomotion, stereotypy (Clineschmidt etal., 1982;Tiedtke etal., 1990;Hoffman, 1992), turning in the Ungerstedt model (Clineschmidt et al, 1982) and cognitive impairments leading to a deficient delayed alternation learning (Schmidt etal., 1988;Hauber and Schmidt, 1990). In addition, prepulse inhibition of the startle response is impaired in rats with systemic injections of dizocilpine or PCP.…”

Section: Introductionmentioning

confidence: 99%

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Clozapine improves dizocilpine-induced delayed alternation impairment in rats

Hauber

1993

J. Neural Transmission

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Summary. The effects of systemic administration of dizocilpine (0.16 mg/kg, i.p.), clozapine (7.5 mg/kg, s.c.) and coadministration of dizocilpine (0.16rag/ kg, i.p.) and clozapine (7.5 mg/kg, s.c.) on acquisition of delayed alternation in a T-maze were tested in rats (N = 7 per group) on six days with 10 choices per day and animal. Clozapine given alone did not impair delayed alternation learnint, except of the first day. Dizocilpine induced a significant delayed alternation impairment on all days tested. Pretreatment with clozapine significantly improved the dizocilpine-induced impairment. Treatment-induced changes of delayed alternation learning and of locomotor activities showed no correlation. The results demonstrate that clozapine functionally compensated for deficits induced by a blockade of the N-methyl-D-asparatate (NMDA) subtype of glutamate receptors.

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Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

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Clozapine improves dizocilpine-induced delayed alternation impairment in rats

Hauber

1993

J. Neural Transmission

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“…This idea is corroborated by the fact that chronic stress reduces basal release of dopamine; in addition, drugs with antidepressant action facilitate the dopaminergic transmission [48]. These results agree with behavioral studies suggesting that behavioral effects of NMDA antagonists are blocked by antipsychotic drugs [49,50]. The action of these drugs in this model made possible the blockade of the symptoms caused by acute administration of ketamine.…”

Section: Discussionsupporting

confidence: 79%

Activities of the Antipsychotic Drugs Haloperidol and Risperidone on Behavioural Effects Induced by Ketamine in Mice

Arruda

2008

Sci. Pharm.

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This study presents the actions of risperidone (Risp) and haloperidol (Hal) on the behavioral effects elicited by ketamine (Ket) on open-field (OF), rota rod (RR) and tail suspension (TS) tests in mice. Male Swiss albino mice (25-30g) were used. Antipsychotics were administered alone (Risp: 0.1 or 0.2 mg/kg, ip; Hal: 0.1 and 0.2 mg/kg, ip) or thirty minutes before Ket (10 mg/Kg, ip). Ket increased (Ket: 63.3 ± 4.2) the locomotor activity compared to control, while neuroleptics decreased it (25.5 ± 4.2). Pretreatment with neuroleptics, in both doses, blocked hyperlocomotion caused by Ket. In RR, Ket decreased (Ket: 15 ± 4.1) the permanence time of the animals compared to control (Control: 59 ± 0.6), but this effect was not observed when neuroleptics were administered alone. Pretreatment with neuroleptics reverted the effect of Ket only in the RR. While Ket (17.3 ± 5.6) decreased the time of immobility in the tail suspension test compared to the control (80.2 ± 10.2), the pretreatment with neuroleptics reverted this mobility. The action of neuroleptics in this model made possible the blockade of the effects caused by acute administration of Ket. Thus, the mechanism of action of ketamine may involve the dopaminergic system.

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“…90,91 In addition, MK-801-induced locomotor activation can be blocked by typical and atypical antipsychotics. [92][93][94] However, certain behavioral responses induced by NMDA antagonists are differentially affected by atyptical drugs. For example, clozapine and olanzapine blocked PCP-induced deficits in social interactions, whereas haloperidol and risperidone were ineffective.…”

Section: Effects Of Typical and Atypical Drugs On Neurotoxicological mentioning

confidence: 99%

Mechanisms of typical and atypical antipsychotic drug action in relation to dopamine and NMDA receptor hypofunction hypotheses of schizophrenia

1999

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Available evidence indicates that clozapine is the most effective antipsychotic currently used for the pharmacotherapy of schizophrenia. Unfortunately, clozapine can cause serious side effects that limit the use of the drug. The therapeutic mechanism of action of clozapine is poorly understood, and accordingly, it has been difficult to design new drugs with the advantageous therapeutic properties of clozapine. Based on hypotheses that dopaminergic and serotonergic receptor-blocking properties of clozapine account for its clinical efficacy, several novel antipsychotic drugs have been introduced recently. There is currently insufficient data to reach definitive conclusions regarding the efficacy of the newer 'atypical' antipsychotics in comparison to clozapine. However, most published studies, and general clinical impressions, suggest that none of the newer drugs are as effective as clozapine in treating patients resistant to typical antipsychotic drug therapy. The present paper briefly reviews the clinical experience with the newer 'atypical' antipsychotic drugs and then discusses clinical and preclinical data potentially relevant to mechanisms of action of clozapine in relation to the NMDA receptor hypofunction hypothesis of schizophrenia.Keywords: clozapine; olanzapine; risperidone; ziprasidone; quetiapine; antipsychotic; schizophrenia; dopamine; NMDA The introduction of clozapine for the pharmacotherapy of schizophrenia represented a significant advance in the treatment of this devastating mental illness. Clozapine is superior to typical neuroleptic drugs (eg haloperidol) in treating positive and negative symptoms, and is effective in many patients who are refractory to typical antipsychotics. [1][2][3] In addition, clozapine does not induce the extrapyramidal side effects (EPS) commonly caused by the typical agents. Because of these properties, clozapine was termed atypical and represents the prototype drug of this class. Although clozapine is the most efficacious antipsychotic currently available, serious side effects induced by the drug, including agranulocytosis, impose substantial limitations on its use. Concerted research and development efforts have been made to produce an antipsychotic drug with the therapeutic advantages of clozapine, without the properties contributing to its serious side effects. However, the specific pharmacological characteristics of clozapine that confer its therapeutic properties are poorly understood. Clozapine binds to a diverse number of neurotransmitter receptors (see Table 1) but it is unclear whether actions at specific serotonin, dopamine, or adrenergic receptors, alone or in combination, account for its clinical efficacy.A number of specific hypotheses concerning mechanisms of action of clozapine have directed drug discovery efforts and led to clinical trials of drugs with widely different receptor-binding characteristics. The clinical experience with drugs whose development was inspired by clozapine will be briefly reviewed and then actions of clozapine and other antip...

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Typical and atypical neuroleptics antagonize MK-801-induced locomotion and stereotypy in rats

Cited by 114 publications

References 32 publications

Clozapine improves dizocilpine-induced delayed alternation impairment in rats

Clozapine improves dizocilpine-induced delayed alternation impairment in rats

Activities of the Antipsychotic Drugs Haloperidol and Risperidone on Behavioural Effects Induced by Ketamine in Mice

Mechanisms of typical and atypical antipsychotic drug action in relation to dopamine and NMDA receptor hypofunction hypotheses of schizophrenia

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