Clozapine and haloperidol produce a differential pattern of immediate early gene expression in rat caudate-putamen, nucleus accumbens, lateral septum and islands of Calleja

MacGibbon, Geraldine; Lawlor, P.; Bravo, Rodrigo; Dragunow, Michael

doi:10.1016/0169-328x(94)90207-0

Cited by 151 publications

(94 citation statements)

References 60 publications

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“…In these areas, as already reported (Deutch and Duman 1996; MacGibbon et al 1994;Merchant et al 1996;Nguyen et al 1992;Robertson and Fibiger 1992;Robertson et al 1994;Wan et al 1995), clozapine, but not haloperidol, increased FLI. Therefore, induction of FLI in the central extended amygdala, such as in the prefrontal cortex, might be a way to differentiate atypical from typical antipsychotics.…”

Section: Fos-like-immunoreactivity After Haloperidolsupporting

confidence: 83%

“…Using this methodology, it has been shown that classical and atypical antipsychotics, such as haloperidol and clozapine, induced the same pattern of FLI in the nucleus accumbens and lateral septum, whereas, they induced a different pattern of FLI in the striatum and prefrontal cortex, which is predictive of their ability to cause extrapyramidal side effects and to be effective on the negative symptoms of schizophrenia (Deutch and Duman 1996;Fibiger 1994;MacGibbon et al 1994;Merchant et al 1996;Nguyen et al 1992;Robertson and Fibiger 1992;Robertson et al 1994;Wan et al 1995).…”

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confidence: 99%

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Differential Induction of Fos-Like-Immunoreactivity in the Extended Amygdala after Haloperidol and Clozapine

Pinna

Morelli

1999

Neuropsychopharmacology

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The extended amygdala is composed of the central and medial amygdaloid nucleus which through the sublenticular extended amygdala (SLEA) and the interstitial nucleus of the posterior limb of the anterior commissure (IPAC) merge into the bed nucleus of stria terminals (BST). Based on anatomical connections with limbic areas, the extended amygdala has been proposed to play an important role in cognitive and affective processes. This study examines the effect of the atypical antipsychotic clozapine and the classical antipsychotic haloperidol on Fos-like-immunoreactivity (FLI) induction in areas belonging to the extended amygdala.Acute administration of clozapine (10-20 mg/kg) The amygdaloid complex is an ensemble of nuclei that play a central role in emotional processes, particularly in the assignment of affective significance to specific stimuli (Aggleton 1993;Aggleton and Mishkin 1985;Gallagher and Chiba 1996;Le Doux 1995). Information elaborated in the basolateral amygdaloid nuclei enter into the central amygdaloid nucleus, which conveys the stimuli together to elicit appropriate behavioral responses (Pitkänen et al. 1997).Neuronal cell groups composing the central and medial amygdaloid nucleus form a continuum of cells that extend through the sublenticular extended amygdala (SLEA) and the interstitial nucleus of the posterior limb of the anterior commissure (IPAC) to merge with the bed nucleus of stria terminalis (BST) and form the socalled extended amygdala (Alheid and Heimer 1988;Alheid et al. 1995;Heimer et al. 1997b).The central division of the extended amygdala, which is formed by the central amygdaloid nucleus, BST lateral division, IPAC, and SLEA central division, establishes reciprocal neuronal connections with the caudal aspect of the nucleus accumbens shell (Acb shell) and is also connected with the prefrontal cortex (de Olmos et al. 1985;Heimer et al. 1997a;Heimer et al. 1997b;Zahm and Brog 1992 Based on anatomical connections, the extended amygdala seems to be an important site involved in neuropsychiatric disorders (Heimer et al. 1997b); however, specific data showing the effect of drugs used in the therapy of these disorders in the extended amygdala are scarce. Induction of the early gene c-fos by antipsychotics in the central amygdaloid nucleus (Sebens et al. 1995) and antagonism of the excitatory effects induced by a local infusion of amphetamine in the amygdaloid complex by clozapine (Wang and Rebec 1996) have been reported. Moreover, it was recently shown (Beck 1994;Duncan et al. 1996;Morelli et al. 1999) that antidepressant drugs inhibiting either noradrenaline or serotonin re-uptake, induced the expression of the early gene c-fos in areas belonging to the rat extended amygdala, suggesting a role of the extended amygdala in disorders characterized by affective disturbance.Induction of the early gene c-fos is secondary to neuronal activation and is correlated to an increased function of specific areas in the CNS (Sagar et al. 1988). Moreover, detection of the c-fos-encoded protein Fos, throug...

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Section: Fos-like-immunoreactivity After Haloperidolsupporting

confidence: 83%

mentioning

confidence: 99%

Differential Induction of Fos-Like-Immunoreactivity in the Extended Amygdala after Haloperidol and Clozapine

Pinna

Morelli

1999

Neuropsychopharmacology

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“…Atypical antipsychotic drugs have a stronger effect in the mesolimbic dopamine system [ventral tegmental area (VTA), PFC, nucleus accumbens], whereas conventional antipsychotic drugs have a stronger effect in the nigrostriatal dopamine system (substantia nigra, striatum). Analysis of Fos expression in rats after treatment with conventional and atypical antipsychotic drugs demonstrates that conventionals induce Fos expression primarily in the striatum and nucleus accumbens, whereas atypical antipsychotic drugs induce Fos expression in the PFC, nucleus accumbens, and the striatum (MacGibbon et al, 1994;Nguyen et al, 1992;Robertson & Fibiger, 1992;Robertson et al, 1994;Sebens et al, 1995;Wan et al, 1995). Studies that measure dopamine-cell depolarization block, the delayed inactivation of dopamine-neuron firing in the mid-brain after treatment with antipsychotic drugs, show a stronger effect in the VTA by atypical antipsychotic drugs and in the substantia nigra by conventional antipsychotic drugs (Grace et al, 1997).…”

Section: Pharmacology Of Antipsychotic Drugsmentioning

confidence: 99%

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Konradi

Heckers

2003

Pharmacology & Therapeutics

295

165

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The glutamate system is involved in many aspects of neuronal synaptic strength and function during development and throughout life. Synapse formation in early brain development, synapse maintenance, and synaptic plasticity are all influenced by the glutamate system. The number of neurons and the number of their connections are determined by the activity of the glutamate system and its receptors. Malfunctions of the glutamate system affect neuroplasticity and can cause neuronal toxicity. In schizophrenia, many glutamate-regulated processes seem to be perturbed. Abnormal neuronal development, abnormal synaptic plasticity, and neurodegeneration have been proposed to be causal or contributing factors in schizophrenia. Interestingly, it seems that the glutamate system is dysregulated and that N-methyl-D-aspartate receptors operate at reduced activity. Here we discuss how the molecular aspects of glutamate malfunction can explain some of the neuropathology observed in schizophrenia, and how the available treatment intervenes through the glutamate system.

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“…Several studies have shown increases in the expression of immediate-early genes (IEGs) after acute drug exposure. [11][12][13][14][15] Many IEGs are known to act as transcriptional regulators, thereby linking receptor-mediated effects to changes in genomic activity. In addition, some studies have examined the expression of candidate genes in animals after chronic exposure to antipsychotic drugs.…”

Section: Introductionmentioning

confidence: 99%

Antipsychotic drug treatment alters expression of mRNAs encoding lipid metabolism-related proteins

et al. 2003

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Using an automated PCR-based genomics approach, TOtal Gene expression Analysis (TOGA s ), we have examined gene expression profiles of mouse striatum and frontal cortex in response to clozapine and haloperidol drug treatment. Of 17 315 mRNAs observed, TOGA s identified several groups of related molecules that were regulated by drug treatment. The expression of some genes encoding proteins involved in neurotransmission, signal transduction, oxidative stress, cell adhesion, apoptosis and proteolysis were altered in the brains of both clozapine-and haloperidol-treated mice as recognized by TOGA s . Most notable was the differential expression of those genes whose products are associated with lipid metabolism. These include apolipoprotein D (apoD), the mouse homolog of oxysterol-binding protein-like protein 8 (OSBPL8), a diacylglycerol receptor (n-chimerin), and lysophosphatidic acid (LPA) acyltransferase. Real-time PCR analysis confirmed increases in the RNA expression of apoD (1.6-2.2-fold) and OSBPL8 (1.7-2.6-fold), and decreases in the RNA expression of nchimerin (1.5-2.2-fold) and LPA acyltransferase (1.5-fold) in response to haloperidol and/or clozapine treatment. Additional molecules related to calcium homeostasis and signal transduction, as well as four sequences of previously unidentified mRNAs, were also confirmed by real-time PCR to be regulated by drug treatment. While antipsychotic drugs may affect several metabolic pathways, lipid metabolism/signaling pathways may be of particular importance in the mechanisms of antipsychotic drug action and in the pathophysiology of psychiatric disorders. Molecular Psychiatry (2003) 8, 983-993.

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Clozapine and haloperidol produce a differential pattern of immediate early gene expression in rat caudate-putamen, nucleus accumbens, lateral septum and islands of Calleja

Cited by 151 publications

References 60 publications

Differential Induction of Fos-Like-Immunoreactivity in the Extended Amygdala after Haloperidol and Clozapine

Differential Induction of Fos-Like-Immunoreactivity in the Extended Amygdala after Haloperidol and Clozapine

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Antipsychotic drug treatment alters expression of mRNAs encoding lipid metabolism-related proteins

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