Haloperidol and clozapine increase neural activity in the rat prefrontal cortex

Kim, Yun Bok; Jang, Jinhwa; Chung, Y.C.; Baeg, Eun Ha; Kim, Hyun Taek; Mook‐Jung, Inhee; Kim, Seung Up; Jung, Min Whan; Chung, Young-Ki

doi:10.1016/s0304-3940(00)01765-1

Cited by 12 publications

(5 citation statements)

References 14 publications

(17 reference statements)

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“…However, despite recent advances [21, 23, 34, 85–89], these symptoms are still poorly characterized in animal models of AD, and their neurobiological substrates remain poorly understood. Previous reports demonstrated that impaired cortical activity and abnormal neuronal morphology in the medial prefrontal cortex may contribute to the emergence of emotional and social interaction disturbances [20, 90, 91]. This suggests that the structural and functional abnormalities induced by PAK inactivation in the frontal cortex of 3xTg-AD mice are involved in AD-associated social changes and support idea that the 3xTg-AD-dnPAK mouse is a model of advanced AD.…”

Section: Discussionsupporting

confidence: 55%

Transgenic autoinhibition of p21-activated kinase exacerbates synaptic impairments and fronto-dependent behavioral deficits in an animal model of Alzheimer’s disease

Bories

Arsenault

Lemire

et al. 2017

Aging

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Defects in p21-activated kinase (PAK) lead to dendritic spine abnormalities and are sufficient to cause cognition impairment. The decrease in PAK in the brain of Alzheimer's disease (AD) patients is suspected to underlie synaptic and dendritic disturbances associated with its clinical expression, particularly with symptoms related to frontal cortex dysfunction. To investigate the role of PAK combined with Aβ and tau pathologies (3xTg-AD mice) in the frontal cortex, we generated a transgenic model of AD with a deficit in PAK activity (3xTg-AD-dnPAK mice). PAK inactivation had no effect on Aβ40 and Aβ42 levels, but increased the phosphorylation ratio of tau in detergent-insoluble protein fractions in the frontal cortex of 18-month-old heterozygous 3xTg-AD mice. Morphometric analyses of layer II/III pyramidal neurons in the frontal cortex showed that 3xTg-AD-dnPAK neurons exhibited significant dendritic attrition, lower spine density and longer spines compared to NonTg and 3xTg-AD mice. Finally, behavioral assessments revealed that 3xTg-AD-dnPAK mice exhibited pronounced anxious traits and disturbances in social behaviors, reminiscent of fronto-dependent symptoms observed in AD. Our results substantiate a critical role for PAK in the genesis of neuronal abnormalities in the frontal cortex underlying the emergence of psychiatric-like symptoms in AD.

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Section: Discussionsupporting

confidence: 55%

Transgenic autoinhibition of p21-activated kinase exacerbates synaptic impairments and fronto-dependent behavioral deficits in an animal model of Alzheimer’s disease

Bories

Arsenault

Lemire

et al. 2017

Aging

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“…Experimental procedures for unit recording in anesthetized animals have been reported previously [ 21 ]. Briefly, animals were deeply anesthetized with urethane (1 g/kg) and one or two tetrodes were lowered into the mPFC (2.7 mm A and 0.6–1.3 mm L to bregma, 2.7–3.3 mm V from the brain surface) at an angle of 10° toward the midline following craniotomy and removal of dura.…”

Section: Methodsmentioning

confidence: 99%

“…Because short interspike intervals (ISIs) contribute more significantly to temporal summation of postsynaptic neurons, only ISIs in the range of tens of milliseconds were considered for burst firing. Based on prior examination of ISI distributions [ 21 ], analysis of burst firing was confined to ISIs within 30 milliseconds. The degree of burst firing was calculated as the proportion ISIs ≤ 30 milliseconds.…”

Section: Methodsmentioning

confidence: 99%

Effects of Methamphetamine on Single Unit Activity in Rat Medial Prefrontal Cortex In Vivo

Jang

Kim

et al. 2007

Neural Plasticity

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To investigate how neuronal activity in the prefrontal cortex changes in an animal model of schizophrenia, we recorded single unit activity in the medial prefrontal cortex of urethane-anesthetized and awake rats following methamphetamine (MA) administration. Systemic MA injection (4 mg/kg, IP) induced inconsistent changes, that is, both enhancement and reduction, in unit discharge rate, with a subset of neurons transiently (<30 min) elevating their activities. The direction of firing rate change was poorly predicted by the mean firing rate or the degree of burst firing during the baseline period. Also, simultaneously recorded units showed opposite directions of firing rate change, indicating that recording location is a poor predictor of the direction of firing rate change. These results raise the possibility that systemic MA injection induces random bidirectional changes in prefrontal cortical unit activity, which may underlie some of MA-induced psychotic symptoms.

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“…This activation has been shown to result from blocking of an inhibitory feedback mechanism via DA D 2 autoreceptors (Chiodo and Bunney 1983). Acute treatment with clozapine or haloperidol also increases the firing rate and burst activity of DA neurons projecting to the PFC (Gessa et al 2000;Kim et al 2001).…”

Section: Acute Apd Treatmentmentioning

confidence: 99%

Regional Differences in the Action of Antipsychotic Drugs: Implications for Cognitive Effects in Schizophrenic Patients

et al. 2010

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Antipsychotic drugs (APDs) have been classified as typical or atypical based on their liability to produce extrapyramidal side effects: atypical APDs are less likely to produce extrapyamidal side effects at therapeutic doses. Evidence from immediate early gene immunohistochemical, electrophysiological, microdialysis, imaging, and behavioral studies suggests that typical APDs preferentially affect the nucleus accumbens (NAc) and the dorsal striatum while atypical APDs preferentially affect the NAc and medial prefrontal cortex (PFC). We review some of this evidence and then discuss studies that have employed cognitive tasks shown previously to depend on dorsal striatal or medial PFC function in schizophrenic patients treated with typical or atypical APDs. Results revealed that patients treated with typical APDs displayed deficits in cognitive tasks that depended on the dorsal striatum but not in tasks that depended on the medial PFC and that those treated with atypical APDs displayed deficits in cognitive tasks that depended on the medial PFC but not in cognitive tasks that depended on the dorsal striatum. These findings suggest that some of the cognitive deficits seen in schizophrenic patients may be related to the medications that are used to treat them.

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Haloperidol and clozapine increase neural activity in the rat prefrontal cortex

Cited by 12 publications

References 14 publications

Transgenic autoinhibition of p21-activated kinase exacerbates synaptic impairments and fronto-dependent behavioral deficits in an animal model of Alzheimer’s disease

Transgenic autoinhibition of p21-activated kinase exacerbates synaptic impairments and fronto-dependent behavioral deficits in an animal model of Alzheimer’s disease

Effects of Methamphetamine on Single Unit Activity in Rat Medial Prefrontal Cortex In Vivo

Regional Differences in the Action of Antipsychotic Drugs: Implications for Cognitive Effects in Schizophrenic Patients

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