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Abdelhamid Benazzouz - One of the best experts on this subject based on the ideXlab platform.
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Involvement of Basal Ganglia Network in Motor Disabilities Induced by Typical Antipsychotics
2013Co-Authors: Jonathan Chetrit, Bérangère Ballion, Steeve Laquitaine, Pauline Belujon, Stéphanie Morin, Anne Taupignon, Bernard Bioulac, Christian E. Gross, Abdelhamid BenazzouzAbstract:Background: Clinical treatments with typical antipsychotic drugs (APDs) are accompanied by extrapyramidal motor sideeffects (EPS) such as hypokinesia and catalepsy. As little is known about electrophysiological substrates of such motor disturbances, we investigated the effects of a typical APD, a-Flupentixol, on the motor behavior and the neuronal activity of the whole basal ganglia nuclei in the rat. Methods and Findings: The motor behavior was examined by the open field actimeter and the neuronal activity of basal ganglia nuclei was investigated using extracellular single unit recordings on urethane anesthetized rats. We show that a-Flupentixol induced EPS paralleled by a decrease in the firing rate and a disorganization of the firing pattern in both substantia nigra pars reticulata (SNr) and subthalamic nucleus (STN). Furthermore, a-Flupentixol induced an increase in the firing rate of globus pallidus (GP) neurons. In the striatum, we recorded two populations of medium spiny neurons (MSNs) after their antidromic identification. At basal level, both striato-pallidal and striato-nigral MSNs were found to be unaffected by a-Flupentixol. However, during electrical cortico-striatal activation only striato-pallidal, but not striato-nigral, MSNs were found to be inhibited by a-Flupentixol. Together, our results suggest that the changes in STN and SNr neuronal activity are a consequence of increased neuronal activity of globus pallidus (GP). Indeed, after selective GP lesion, a-Flupentixol failed to induce EPS and to alter STN neuronal activity
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α-Flupentixol alters the firing patterns of substantia nigra pars reticulata neurons.
2013Co-Authors: Jonathan Chetrit, Bérangère Ballion, Steeve Laquitaine, Pauline Belujon, Stéphanie Morin, Anne Taupignon, Bernard Bioulac, Christian E. Gross, Abdelhamid BenazzouzAbstract:(A and B) Sections of extracellular recordings of action potentials, before and after injection respectively, showing that α-Flupentixol reduced the firing rate and made the pattern irregular. (C and D) Interspike interval histograms, (E and F) density histograms, respectively before and after α-Flupentixol injection confirming the disorganization of the firing pattern induced by α-Flupentixol in the same neuron.
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α-Flupentixol alters the firing patterns of subthalamic nucleus neurons.
2013Co-Authors: Jonathan Chetrit, Bérangère Ballion, Steeve Laquitaine, Pauline Belujon, Stéphanie Morin, Anne Taupignon, Bernard Bioulac, Christian E. Gross, Abdelhamid BenazzouzAbstract:(A and B) Sections of extracellular recordings of action potentials, before and after injection respectively, showing that α-Flupentixol reduced the firing rate and made the pattern irregular. (C and D) Interspike interval histograms, (E and F) density histograms, respectively before and after α-Flupentixol injection confirming the disorganization of the firing pattern induced by α-Flupentixol in the same neuron.
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α-Flupentixol induces hypomotor activity and catalepsy.
2013Co-Authors: Jonathan Chetrit, Bérangère Ballion, Steeve Laquitaine, Pauline Belujon, Stéphanie Morin, Anne Taupignon, Bernard Bioulac, Christian E. Gross, Abdelhamid BenazzouzAbstract:(A–C) Histograms illustrating the scored motor activity recorded during the second 10 minutes session fifty minutes after the injection of saline (control) or α-Flupentixol (0.3 mg/kg) or saline on day 4, 5 and 6 respectively. Note that α-Flupentixol induced a significant decrease of the scored horizontal activity (A), vertical activity (B) and stereotypic movements (C) in comparison with controls (n = 10 rats) (Wilcoxon test, **p0.05). (D) Histogram displaying the evolution of catalepsy induced by the injection of α-Flupentixol. Measurement of the latency from paw placement until the first complete removal of one paw from the bar during the catalepsy test. Values are presented as the mean±S.E.M. cts/10 min = counts/10 minutes.
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α-Flupentixol does not alter the firing patterns of globus pallidus neurons in vivo.
2013Co-Authors: Jonathan Chetrit, Bérangère Ballion, Steeve Laquitaine, Pauline Belujon, Stéphanie Morin, Anne Taupignon, Bernard Bioulac, Christian E. Gross, Abdelhamid BenazzouzAbstract:(A and B) Sections of extracellular recordings before and after injection respectively, showing that α-Flupentixol increased the firing rate without modifying the firing pattern. (C and D) Interspike interval histograms, (E and F) density histograms, respectively before and after α-Flupentixol injection confirming the absence of changes of the firing pattern in the same neuron.
Jonathan Chetrit - One of the best experts on this subject based on the ideXlab platform.
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Involvement of Basal Ganglia Network in Motor Disabilities Induced by Typical Antipsychotics
2013Co-Authors: Jonathan Chetrit, Bérangère Ballion, Steeve Laquitaine, Pauline Belujon, Stéphanie Morin, Anne Taupignon, Bernard Bioulac, Christian E. Gross, Abdelhamid BenazzouzAbstract:Background: Clinical treatments with typical antipsychotic drugs (APDs) are accompanied by extrapyramidal motor sideeffects (EPS) such as hypokinesia and catalepsy. As little is known about electrophysiological substrates of such motor disturbances, we investigated the effects of a typical APD, a-Flupentixol, on the motor behavior and the neuronal activity of the whole basal ganglia nuclei in the rat. Methods and Findings: The motor behavior was examined by the open field actimeter and the neuronal activity of basal ganglia nuclei was investigated using extracellular single unit recordings on urethane anesthetized rats. We show that a-Flupentixol induced EPS paralleled by a decrease in the firing rate and a disorganization of the firing pattern in both substantia nigra pars reticulata (SNr) and subthalamic nucleus (STN). Furthermore, a-Flupentixol induced an increase in the firing rate of globus pallidus (GP) neurons. In the striatum, we recorded two populations of medium spiny neurons (MSNs) after their antidromic identification. At basal level, both striato-pallidal and striato-nigral MSNs were found to be unaffected by a-Flupentixol. However, during electrical cortico-striatal activation only striato-pallidal, but not striato-nigral, MSNs were found to be inhibited by a-Flupentixol. Together, our results suggest that the changes in STN and SNr neuronal activity are a consequence of increased neuronal activity of globus pallidus (GP). Indeed, after selective GP lesion, a-Flupentixol failed to induce EPS and to alter STN neuronal activity
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α-Flupentixol alters the firing patterns of substantia nigra pars reticulata neurons.
2013Co-Authors: Jonathan Chetrit, Bérangère Ballion, Steeve Laquitaine, Pauline Belujon, Stéphanie Morin, Anne Taupignon, Bernard Bioulac, Christian E. Gross, Abdelhamid BenazzouzAbstract:(A and B) Sections of extracellular recordings of action potentials, before and after injection respectively, showing that α-Flupentixol reduced the firing rate and made the pattern irregular. (C and D) Interspike interval histograms, (E and F) density histograms, respectively before and after α-Flupentixol injection confirming the disorganization of the firing pattern induced by α-Flupentixol in the same neuron.
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α-Flupentixol alters the firing patterns of subthalamic nucleus neurons.
2013Co-Authors: Jonathan Chetrit, Bérangère Ballion, Steeve Laquitaine, Pauline Belujon, Stéphanie Morin, Anne Taupignon, Bernard Bioulac, Christian E. Gross, Abdelhamid BenazzouzAbstract:(A and B) Sections of extracellular recordings of action potentials, before and after injection respectively, showing that α-Flupentixol reduced the firing rate and made the pattern irregular. (C and D) Interspike interval histograms, (E and F) density histograms, respectively before and after α-Flupentixol injection confirming the disorganization of the firing pattern induced by α-Flupentixol in the same neuron.
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α-Flupentixol induces hypomotor activity and catalepsy.
2013Co-Authors: Jonathan Chetrit, Bérangère Ballion, Steeve Laquitaine, Pauline Belujon, Stéphanie Morin, Anne Taupignon, Bernard Bioulac, Christian E. Gross, Abdelhamid BenazzouzAbstract:(A–C) Histograms illustrating the scored motor activity recorded during the second 10 minutes session fifty minutes after the injection of saline (control) or α-Flupentixol (0.3 mg/kg) or saline on day 4, 5 and 6 respectively. Note that α-Flupentixol induced a significant decrease of the scored horizontal activity (A), vertical activity (B) and stereotypic movements (C) in comparison with controls (n = 10 rats) (Wilcoxon test, **p0.05). (D) Histogram displaying the evolution of catalepsy induced by the injection of α-Flupentixol. Measurement of the latency from paw placement until the first complete removal of one paw from the bar during the catalepsy test. Values are presented as the mean±S.E.M. cts/10 min = counts/10 minutes.
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α-Flupentixol does not alter the firing patterns of globus pallidus neurons in vivo.
2013Co-Authors: Jonathan Chetrit, Bérangère Ballion, Steeve Laquitaine, Pauline Belujon, Stéphanie Morin, Anne Taupignon, Bernard Bioulac, Christian E. Gross, Abdelhamid BenazzouzAbstract:(A and B) Sections of extracellular recordings before and after injection respectively, showing that α-Flupentixol increased the firing rate without modifying the firing pattern. (C and D) Interspike interval histograms, (E and F) density histograms, respectively before and after α-Flupentixol injection confirming the absence of changes of the firing pattern in the same neuron.
Zbigniew S. Herman - One of the best experts on this subject based on the ideXlab platform.
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Flupentixol AND TRIFLUPERIDOL REDUCE INTERLEUKIN-1 � AND INTERLEUKIN-2 RELEASE BY RAT MIXED GLIAL AND
2013Co-Authors: Pol J. Pharmacol, Microglial Cell Cultures, Jan Kowalski, Krzysztof Labuzek, Zbigniew S. HermanAbstract:Flupentixol and trifluperidol reduce interleukin-1β and interleukin-2 release by rat mixed glial and microglial cell cultures. J. KOWALSKI, K. LABUZEK, Z.S. HERMAN. Pol. J. Pharmacol., 2004, 56, 563–570. Neuroleptics penetrate into the brain, where they act not only on neurons but probably also on glial cells. In the available literature, there are no reports on the effect of neuroleptics on cytokine release in glia cultures. The aim of this study was to evaluate the effect of neuroleptics on the release of proinflammatory cytokines (IL-1 � and IL-2) by mixed glial and microglial cell cultures. Trifluperidol at 20 and 2 �M reduced IL- � secretion by mixed glial cultures after 3 days of exposure. Trifluperidol at 20, 2 and 0.2 �M diminished IL- � secretion after 1 day of incubation. Trifluperidol at 20 and 2 �M reduced IL-2 release after 1 and 3 days of exposure. Flupentixol at 20 and 2 �M reduced IL-1 � by mixed glial cell cultures after 3 days of exposure. Flupentixol at 20, 2 and 0.2 �M caused diminution of IL-1 � release after 1 day of exposure. Flupentixol at 20 and 2 �M reduced IL-2 release after 1 day of incubation. Flupentixol at 20, 2 and 0.2 �M diminished IL-2 release after 3 days of exposure. Flupentixol at 20, 10, 2 and 0.2 �M reduced IL-1� release by microgial cell cultures. Flupentixol at 20, 10 and 2 �M reduced release of IL-2 by microglial cells after 1 day of exposure. The results of the present study suggest that neuroleptics have an inhibiting effect on the release of glial cytokines, but clinical significance this results remains to be elucidated
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Flupentixol and trifluperidol reduce interleukin-1 beta and interleukin-2 release by rat mixed glial and microglial cell cultures.
Polish Journal of Pharmacology, 2004Co-Authors: Jan Kowalski, Krzysztof Labuzek, Zbigniew S. HermanAbstract:: Neuroleptics penetrate into the brain, where they act not only on neurons but probably also on glial cells. In the available literature, there are no reports on the effect of neuroleptics on cytokine release in glia cultures. The aim of this study was to evaluate the effect of neuroleptics on the release of proinflammatory cytokines (IL-1beta and IL-2) by mixed glial and microglial cell cultures. Trifluperidol at 20 and 2 muM reduced IL-beta secretion by mixed glial cultures after 3 days of exposure. Trifluperidol at 20, 2 and 0.2 muM diminished IL-beta secretion after 1 day of incubation. Trifluperidol at 20 and 2 muM reduced IL-2 release after 1 and 3 days of exposure. Flupentixol at 20 and 2 muM reduced IL-1beta by mixed glial cell cultures after 3 days of exposure. Flupentixol at 20, 2 and 0.2 muM caused diminution of IL-1beta release after 1 day of exposure. Flupentixol at 20 and 2 muM reduced IL-2 release after 1 day of incubation. Flupentixol at 20, 2 and 0.2 muM diminished IL-2 release after 3 days of exposure. Flupentixol at 20, 10, 2 and 0.2 muM reduced IL-1beta release by microgial cell cultures. Flupentixol at 20, 10 and 2 muM reduced release of IL-2 by microglial cells after 1 day of exposure. The results of the present study suggest that neuroleptics have an inhibiting effect on the release of glial cytokines, but clinical significance this results remains to be elucidated.
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Flupentixol and trifluperidol reduce secretion of tumor necrosis factor-α and nitric oxide by rat microglial cells
Neurochemistry international, 2003Co-Authors: Jan Kowalski, Krzysztof Labuzek, Zbigniew S. HermanAbstract:Abstract Tumor necrosis factor-α (TNF-α) and nitric oxide (NO), both of which are produced by activated microglial cells, are involved in the neuropathogenesis of many diseases affecting the central nervous system (CNS). There is a need to develop drugs that inhibit neurotoxic processes in neurodegenerative diseases. The aim of this study was to evaluate the effect of two neuroleptics, Flupentixol and trifluperidol, on the release of pro-apoptotic TNF-α and NO by LPS-activated rat microglial cells. Flupentixol and trifluperidol reduced the TNF-α and NO release by cultured microglia exposed to LPS for 6 and 24 h. The results suggest that Flupentixol and trifluperidol, which are well-known antipsychotic drugs, may be used in the treatment of CNS diseases associated with excessive TNF-α and NO release.
Gudrun Høiseth - One of the best experts on this subject based on the ideXlab platform.
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impact of cyp2d6 on serum concentrations of Flupentixol haloperidol perphenazine and zuclopenthixol
British Journal of Clinical Pharmacology, 2020Co-Authors: Ragnhild Birkeland Waade, Vigdis Solhaug, Gudrun HøisethAbstract:AIMS To investigate the impact of cytochrome P450 2D6 (CYP2D6) on dose-adjusted serum concentrations of Flupentixol, haloperidol, perphenazine and zuclopenthixol in a therapeutic drug monitoring (TDM) cohort of psychiatric patients. We also especially studied the functional impact of CYP2D6*41 on dose-adjusted serum concentrations in the perphenazine-treated patients. METHODS Serum concentrations of Flupentixol, haloperidol, perphenazine and zuclopenthixol from CYP-genotyped patients were extracted retrospectively from a routine TDM database in the period March 2005 to May 2019. Samples were divided into three CYP2D6 phenotype subgroups according to genotype; normal metabolizers (NMs), intermediate metabolizers (IMs) and poor metabolizers (PMs). The effect of CYP2D6 phenotype on dose-adjusted serum concentrations of the four antipsychotics was evaluated by multivariable mixed model analyses. RESULTS Mean dose-adjusted serum concentrations of perphenazine (564 samples) were 3.9-fold and 1.6-fold higher in CYP2D6 PMs and IMs, respectively, compared with NMs (p<0.001 and p<0.01). For zuclopenthixol (658 samples), mean dose-adjusted serum concentrations were about 1.5-fold and 1.3-fold higher in CYP2D6 PMs and IMs, respectively, compared with NMs (p<0.01 and p<0.001). CYP2D6 was of minor or no importance to haloperidol (320 samples) and Flupentixol (115 samples). In our data material, the genotype CYP2D6 *1/*41 appears to have a similar impact on dose-adjusted serum concentrations of perphenazine as *1/null (null = variant allele encoding no enzyme function). CONCLUSIONS This study shows that CYP2D6 is important for the metabolism of perphenazine and zuclopenthixol, but not for haloperidol and Flupentixol. The CYP2D6*41 allele appears to have a reduced function close to non-functional variant alleles.
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Impact of CYP2D6 on serum concentrations of Flupentixol, haloperidol, perphenazine and zuclopenthixol
British journal of clinical pharmacology, 2020Co-Authors: Ragnhild Birkeland Waade, Vigdis Solhaug, Gudrun HøisethAbstract:AIMS To investigate the impact of cytochrome P450 2D6 (CYP2D6) on dose-adjusted serum concentrations of Flupentixol, haloperidol, perphenazine and zuclopenthixol in a therapeutic drug monitoring (TDM) cohort of psychiatric patients. We also studied the functional impact of CYP2D6*41 on dose-adjusted serum concentrations in the perphenazine-treated patients. METHODS Serum concentrations of Flupentixol, haloperidol, perphenazine and zuclopenthixol from CYP-genotyped patients were extracted retrospectively from a routine TDM database in the period March 2005 to May 2019. Samples were divided into three CYP2D6 phenotype subgroups according to genotype; normal metabolizers (NMs), intermediate metabolizers (IMs) and poor metabolizers (PMs). The effect of CYP2D6 phenotype on dose-adjusted serum concentrations of the four antipsychotics was evaluated by multivariable mixed model analyses. RESULTS Mean dose-adjusted serum concentrations of perphenazine (564 samples) were 3.9-fold and 1.6-fold higher in CYP2D6 PMs and IMs, respectively, compared with NMs (P < .001 and P < .01). For zuclopenthixol (658 samples), mean dose-adjusted serum concentrations were about 1.5-fold and 1.3-fold higher in CYP2D6 PMs and IMs, respectively, compared with NMs (P < .01 and P < .001). CYP2D6 was of minor or no importance to haloperidol (320 samples) and Flupentixol (115 samples). In our data material, the genotype CYP2D6 *1/*41 appears to have a similar impact on dose-adjusted serum concentrations of perphenazine as *1/null (null = variant allele encoding no enzyme function). CONCLUSIONS This study shows that CYP2D6 is important for the metabolism of perphenazine and zuclopenthixol, but not for haloperidol and Flupentixol. The CYP2D6*41 allele appears to have a reduced function close to nonfunctional variant alleles.
Christian E. Gross - One of the best experts on this subject based on the ideXlab platform.
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Involvement of Basal Ganglia Network in Motor Disabilities Induced by Typical Antipsychotics
2013Co-Authors: Jonathan Chetrit, Bérangère Ballion, Steeve Laquitaine, Pauline Belujon, Stéphanie Morin, Anne Taupignon, Bernard Bioulac, Christian E. Gross, Abdelhamid BenazzouzAbstract:Background: Clinical treatments with typical antipsychotic drugs (APDs) are accompanied by extrapyramidal motor sideeffects (EPS) such as hypokinesia and catalepsy. As little is known about electrophysiological substrates of such motor disturbances, we investigated the effects of a typical APD, a-Flupentixol, on the motor behavior and the neuronal activity of the whole basal ganglia nuclei in the rat. Methods and Findings: The motor behavior was examined by the open field actimeter and the neuronal activity of basal ganglia nuclei was investigated using extracellular single unit recordings on urethane anesthetized rats. We show that a-Flupentixol induced EPS paralleled by a decrease in the firing rate and a disorganization of the firing pattern in both substantia nigra pars reticulata (SNr) and subthalamic nucleus (STN). Furthermore, a-Flupentixol induced an increase in the firing rate of globus pallidus (GP) neurons. In the striatum, we recorded two populations of medium spiny neurons (MSNs) after their antidromic identification. At basal level, both striato-pallidal and striato-nigral MSNs were found to be unaffected by a-Flupentixol. However, during electrical cortico-striatal activation only striato-pallidal, but not striato-nigral, MSNs were found to be inhibited by a-Flupentixol. Together, our results suggest that the changes in STN and SNr neuronal activity are a consequence of increased neuronal activity of globus pallidus (GP). Indeed, after selective GP lesion, a-Flupentixol failed to induce EPS and to alter STN neuronal activity
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α-Flupentixol alters the firing patterns of substantia nigra pars reticulata neurons.
2013Co-Authors: Jonathan Chetrit, Bérangère Ballion, Steeve Laquitaine, Pauline Belujon, Stéphanie Morin, Anne Taupignon, Bernard Bioulac, Christian E. Gross, Abdelhamid BenazzouzAbstract:(A and B) Sections of extracellular recordings of action potentials, before and after injection respectively, showing that α-Flupentixol reduced the firing rate and made the pattern irregular. (C and D) Interspike interval histograms, (E and F) density histograms, respectively before and after α-Flupentixol injection confirming the disorganization of the firing pattern induced by α-Flupentixol in the same neuron.
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α-Flupentixol alters the firing patterns of subthalamic nucleus neurons.
2013Co-Authors: Jonathan Chetrit, Bérangère Ballion, Steeve Laquitaine, Pauline Belujon, Stéphanie Morin, Anne Taupignon, Bernard Bioulac, Christian E. Gross, Abdelhamid BenazzouzAbstract:(A and B) Sections of extracellular recordings of action potentials, before and after injection respectively, showing that α-Flupentixol reduced the firing rate and made the pattern irregular. (C and D) Interspike interval histograms, (E and F) density histograms, respectively before and after α-Flupentixol injection confirming the disorganization of the firing pattern induced by α-Flupentixol in the same neuron.
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α-Flupentixol induces hypomotor activity and catalepsy.
2013Co-Authors: Jonathan Chetrit, Bérangère Ballion, Steeve Laquitaine, Pauline Belujon, Stéphanie Morin, Anne Taupignon, Bernard Bioulac, Christian E. Gross, Abdelhamid BenazzouzAbstract:(A–C) Histograms illustrating the scored motor activity recorded during the second 10 minutes session fifty minutes after the injection of saline (control) or α-Flupentixol (0.3 mg/kg) or saline on day 4, 5 and 6 respectively. Note that α-Flupentixol induced a significant decrease of the scored horizontal activity (A), vertical activity (B) and stereotypic movements (C) in comparison with controls (n = 10 rats) (Wilcoxon test, **p0.05). (D) Histogram displaying the evolution of catalepsy induced by the injection of α-Flupentixol. Measurement of the latency from paw placement until the first complete removal of one paw from the bar during the catalepsy test. Values are presented as the mean±S.E.M. cts/10 min = counts/10 minutes.
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α-Flupentixol does not alter the firing patterns of globus pallidus neurons in vivo.
2013Co-Authors: Jonathan Chetrit, Bérangère Ballion, Steeve Laquitaine, Pauline Belujon, Stéphanie Morin, Anne Taupignon, Bernard Bioulac, Christian E. Gross, Abdelhamid BenazzouzAbstract:(A and B) Sections of extracellular recordings before and after injection respectively, showing that α-Flupentixol increased the firing rate without modifying the firing pattern. (C and D) Interspike interval histograms, (E and F) density histograms, respectively before and after α-Flupentixol injection confirming the absence of changes of the firing pattern in the same neuron.