Behavioural, pharmacological and biochemical effects of acute and chronic administration of ketamine in the rat

Lannes, Béatrice; Micheletti, Gabriele; Warter, Jean‐Marie; Kempf, E.; Scala, Georges Di

doi:10.1016/0304-3940(91)90255-r

Cited by 51 publications

(24 citation statements)

References 32 publications

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“…These data are consistent with the previous finding that repeated exposure to ketamine, a PCP congener, enhances apomorphine-induced stereotypy in rats (Lannes et al 1991). Augmented behavioral effects of a direct dopamine receptor agonist would suggest that postsynaptic dopaminergic function may likewise be enhanced and that dorsal striatal function may also be enhanced, because stereotypy is most closely associated with the nigrostriatal dopaminergic innervation of dorsal striatum.…”

Section: Discussionsupporting

confidence: 91%

“…Subcortical dopaminergic hyper-responsivity may, thus, be expressed along with cortical dopaminergic hypoactivity in subchronic PCP-treated subjects. This hypothesis is preliminarily supported by the finding that chronic ketamine administration leads to increased apomorphine-induced stereotypy in rats (Lannes et al 1991).In the present report, we describe the results of experiments designed to test the hypothesis that long-term administration of PCP results in subcortical dopaminergic hyperactivity along with enduring deficits in cortical dopaminergic transmission. We tested whether subchronic PCP administration augmented the locomotor response to amphetamine and stress and to haloperidolstimulated increases in mesolimbic dopamine utilization.…”

mentioning

confidence: 56%

Section: Previous Studies Have Shown That Repeated Exposures To Phencmentioning

confidence: 77%

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Subchronic Phencyclidine Administration Increases Mesolimbic Dopaminergic System Responsivity and Augments Stress- and Psychostimulant-Induced Hyperlocomotion

Jentsch

Taylor

Roth

1998

Neuropsychopharmacology

147

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Previous studies have shown that repeated exposures to phencyclidine (PCP) induces prefrontal cortical dopaminergic and cognitive deficits in rats and (Javitt and Zukin 1991); that is, administration of PCP or its congeners ketamine or dizocilpine can induce schizophrenic-like symptomatology in people (Luby et al. 1959;Krystal et al. 1994; Bunney et al. 1994) and precipitate psychosis in schizophrenics (Ital et al. 1967;Lahti et al. 1994). These compounds can stimulate both positive and negative symptoms of schizophrenia (Javitt and Zukin), including cognitive dysfunction (Cosgrove and Newell 1991). As such, PCP administration has been suggested to represent a drug-induced model of schizophrenia (Javitt and Zukin;Steinpreis 1996).The ability of PCP to simulate the symptomatology of schizophrenia in humans has led to the proposal that the behavioral pathologies evident in schizophrenia and PCP-exposed humans are caused by dysfunction of common neural substrates (Luby et al. 1959;Javitt and Zukin 1991). The effects of PCP on brain dopamine systems has received particular attention (Meltzer et al. 1980;Bowers and Hoffman 1984;Deutch et al. 1987;Hertel et al. 1996;Jentsch et al. 1997a) since alterations in dopaminergic systems have been hypothesized in schizophrenia (reviewed in Davis et al. 1991;Deutch 1992 Recent work has shown that long-term administration of PCP causes enduring cognitive dysfunction and cortical dopamine deficits in rats and monkeys (Jentsch et al. 1997b,c). These data correspond to reports of cognitive disturbances in schizophrenic subjects (Fey 1951;Goldman-Rakic 1991;Park and Holzman 1992), and recent in vivo imaging studies of the schizophrenic brain have revealed a failure of activation of frontal cortex during cognitive performance (termed "hypofrontality" by Weinberger and Berman 1996), effects that may be mediated by dopaminergic dysfunction Daniel et al. 1989 Daniel et al. , 1991Dolan et al. 1995). These data are also consistent with studies in nonhuman primates that have revealed that lesions of the prefrontal cortical dopamine innervation lead to working memory impairments (Brozoski et al. 1979), a cognitive process closely associated with this brain region (Goldman-Rakic 1987).Moreover, prefrontal cortical dopaminergic deficiencies may result in enhancement of activity of subcortical dopamine systems. Destruction of prefrontal cortical dopamine terminals has been shown to augment the response of the mesolimbic dopamine systems to stress ), amphetamine sensitization (Banks and Gratton 1994), high K ϩ -stimulation (Roberts et al. 1994), or haloperidol administration (Rosin et al. 1994). These data have supported an emerging neurochemical hypothesis of schizophrenia: cortical dopaminergic hypoactivity and subcortical dopaminergic hyperactivity (Robbins 1990;Grace 1991;Deutch 1992). Recent in vivo studies of the schizophrenic brain have revealed evidence for the subcortical component of this hypothesis; heightened responsivity to the dopamine-releasing properties of amphetamine ha...

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 56%

Section: Previous Studies Have Shown That Repeated Exposures To Phencmentioning

confidence: 77%

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Subchronic Phencyclidine Administration Increases Mesolimbic Dopaminergic System Responsivity and Augments Stress- and Psychostimulant-Induced Hyperlocomotion

Jentsch

Taylor

Roth

1998

Neuropsychopharmacology

147

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“…Augmented locomotor responsivity to stress and d-amphetamine has been reported after long-term PCP exposure (Jentsch et al 1998c), and subchronic ketamine administration has been shown to increase apomorphine-induced stereotypy (Lannes et al 1991). Furthermore, we have observed that subchronic PCP exposure leads to an increased mesolimbic dopamine response after an acute administration of haloperidol (Jentsch et al 1998c).…”

Section: Effects Of Long-term Pcp Administration On Noncognitive Behasupporting

confidence: 69%

“…PCP-induced sensitization of limbic circuits might have relevance to the neurobiology of schizophrenia, as sensitization to the locomotorstimulating effects of PCP, ketamine, and MK-801 has been reported (Scalzo and Holson 1992;Wolf and Khansa 1991;Xu and Domino 1994). Importantly, this phenomenon seems to be very dose and regimen sensitive and may be complicated by tolerance to the ataxic effects of PCP (Melnick et al 1997).Augmented locomotor responsivity to stress and d-amphetamine has been reported after long-term PCP exposure (Jentsch et al 1998c), and subchronic ketamine administration has been shown to increase apomorphine-induced stereotypy (Lannes et al 1991). Furthermore, we have observed that subchronic PCP exposure leads to an increased mesolimbic dopamine response after an acute administration of haloperidol (Jentsch et al 1998c).…”

mentioning

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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Effect of reserpine-induced depletion of synaptic dopamine on [11C]Raclopride binding to D2-dopamine receptors in the monkey brain

Ginovart

Farde

Halldin

et al. 1997

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Positron emission tomography was used to examine the in vivo binding of [11C]raclopride to D2-dopamine (DA) receptors in the striatum of two Cynomolgus monkeys after a single dose of reserpine (1 mg/kg, i.v.). A Scatchard procedure was repeated five times to follow D2 receptor density and apparent affinity for 7 weeks after reserpine. Reserpine-induced depletion of DA lead to a marked increase in [11C]raclopride binding, which was still detectable 20 days after treatment. Scatchard analyses indicated that the measured increase in [11C]raclopride binding reflected an increase in receptor affinity but no evident change in receptor density (Bmax). Thus, the increase in [11C]raclopride binding after reserpine should correspond to a reduced competition with endogenous DA for binding to D2 receptors. The results were used to estimate the DA-induced D2 occupancy to be about 40% at physiological conditions.

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Behavioural, pharmacological and biochemical effects of acute and chronic administration of ketamine in the rat

Cited by 51 publications

References 32 publications

Subchronic Phencyclidine Administration Increases Mesolimbic Dopaminergic System Responsivity and Augments Stress- and Psychostimulant-Induced Hyperlocomotion

Subchronic Phencyclidine Administration Increases Mesolimbic Dopaminergic System Responsivity and Augments Stress- and Psychostimulant-Induced Hyperlocomotion

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

Effect of reserpine-induced depletion of synaptic dopamine on [11C]Raclopride binding to D2-dopamine receptors in the monkey brain

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