Cholinergic Hyperactivity and Negative Schizophrenic Symptoms

Tandon, Rajiv; Greden, John F.

doi:10.1001/archpsyc.1989.01810080075010

Cited by 335 publications

(43 citation statements)

References 105 publications

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“…While drug discrimination procedures have become an increasingly important preclinical test in the development of new drugs, it is not yet clear as to whether or not the discriminative stimulus properties of antipsychotic drugs are related to their therapeutic effects. The fact that serotonergic and cholinergic effects are important in the discriminative stimulus properties of antipsychotic drugs is encouraging, as both of these receptor systems have been implicated in the neuropathology of schizophrenia (Snyder et al 1974;Bleich et al 1988;Meltzer 1989Tandon and Greden 1989;Iqbal et al 1993;Borison 1995) and both may prove to be important for olanzapine's and clozapine's unique profiles as atypical antipsychotic drugs.…”

Section: Discussionmentioning

confidence: 99%

The discriminative stimulus properties of the atypical antipsychotic olanzapine in rats

Porter¹,

McCallum²,

Varvel³

et al. 2000

Psychopharmacology

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In contrast to previous discrimination studies with clozapine-trained rats, the typical antipsychotic agents chlorpromazine and thioridazine and the serotonin antagonist ritanserin substituted for olanzapine. These results demonstrate that there are differences in the mechanisms underlying the discriminative stimulus properties of clozapine and olanzapine. Specifically, olanzapine's discriminative stimulus properties appear to be meditated in part by both cholinergic and serotonergic mechanisms.

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Section: Discussionmentioning

confidence: 99%

The discriminative stimulus properties of the atypical antipsychotic olanzapine in rats

Porter¹,

McCallum²,

Varvel³

et al. 2000

Psychopharmacology

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“…Moreover, a hypercholinergic hypothesis of the negative symptoms of schizophrenia has been promoted (Tandon and Greden 1989). Acute administration of PCP to rats seems to increase acetylcholinergic transmission profoundly (as revealed by a hypercholinergic mechanism in the neurotoxic effects of PCP, Olney et al 1991).…”

Section: Cholinergic Dysfunctionmentioning

confidence: 99%

The Neuropsychopharmacology of Phencyclidine From NMDA Receptor Hypofunction to the Dopamine Hypothesis of Schizophrenia

Jentsch

Roth²

1999

Neuropsychopharmacology

1,210

772

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Administration of noncompetitive NMDA ր glutamate receptor antagonists, such as phencyclidine (PCP) and ketamine, to humans induces a broad range of schizophrenic-like symptomatology, findings that have contributed to a hypoglutamatergic hypothesis of schizophrenia. Moreover, a history of experimental investigations of the effects of these drugs in animalsBiological psychiatric research has seen the development of many putative animal models of schizophrenia. The etiological bases of these models have varied widely from the administration of purportedly psychotomimetic drugs (Snyder 1988; Javitt and Zukin 1991; Jentsch et al. 1998a), to perinatal insults (Lipska et al. 1993;El-Khodor and Boksa 1997;Moore and Grace 1997; Bertolino et al. 1997), to chronic social isolation or stress (Jones et al. 1990), and beyond. The administration of psychotomimetic drugs to humans and animals represents probably the most widely accepted and utilized class of schizophrenia models. These "pharmacological" models seem to represent methods for the induction of psychopathology in humans and aberrant (potentially related) behavior in animals.At the behavioral level, there seems to be some heterogeneity in the effects of different psychotomimetic drug classes. The psychomotor stimulants, such as amphetamine and cocaine, can clearly induce a form of 20 , NO . 3 paranoid psychosis in human subjects after high-dose or long-term administration, but evidence regarding the ability of these agents to induce "deficit" state symptoms is conflicting (Angrist and Gershon 1970;Everitt et al., 1997); moreover, there is evidence that amphetamine may actually alleviate negative and cognitive symptoms in schizophrenic patients (Angrist et al. 1982;Goldberg et al. 1991; Carter et al. 1997). Psychotomimetic indoleamines, such as lysergic acid diethylamide, can induce profound sensory hallucinations without causing any apparent deficit state in normal subjects (Geyer and Markou 1994) and without precipitating symptomatology in schizophrenic patients (Cohen et al. 1962). In contrast, the noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) ր glutamate receptor, including phencyclidine (PCP) and ketamine, seem to be capable of inducing both positive and negative symptoms of schizophrenia, including cognitive dysfunction in normal humans (Snyder 1980; Javitt and Zukin 1991;Tamminga 1998); these drugs also profoundly exacerbate both positive and negative symptoms in schizophrenic patients (Itil et al. 1967;Lahti et al. 1994;Malhotra et al. 1997a).Because of the more comprehensive psychopathology induced by PCP, many researchers have studied the effects of NMDA receptor antagonists in humans and animals to gain insights into the neurobiology of schizophrenia. In this review, the validity of NMDA receptor antagonist-induced models of schizophrenia in humans and animals are considered, and the applicability of acute versus chronic administration of PCP as a more precise model is assessed. The neurobiological substrates of the observed behavior...

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“…Antiparkinsonian medication is another option, especially in conjunction with risperidone for the same reason. Anticholinergic antiparkinsonian medication may be an interesting option as well, since it is possible that it has its own antidepressant activity (27,134) or anti-negative-symptom action (135). However, an anticholinergic antiparkinsonian agent would not be likely to be a felicitous choice in a patient receiving clozapine, since the combined anticholinergic activity might lead to too great a risk of autonomic side effects.…”

Section: Treatment Strategiesmentioning

confidence: 99%

Depression in Schizophrenia: Perspective in the Era of “Atypical” Antipsychotic Agents

Siris

2000

AJP

382

244

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Cholinergic Hyperactivity and Negative Schizophrenic Symptoms

Cited by 335 publications

References 105 publications

The discriminative stimulus properties of the atypical antipsychotic olanzapine in rats

The discriminative stimulus properties of the atypical antipsychotic olanzapine in rats

The Neuropsychopharmacology of Phencyclidine From NMDA Receptor Hypofunction to the Dopamine Hypothesis of Schizophrenia

Depression in Schizophrenia: Perspective in the Era of “Atypical” Antipsychotic Agents

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