Prozac-induced changes not readily reversible

[Guest guest]

"...They previously showed that fluoxetine could reverse the state of maturation of hippocampal granule cells in adult mice. This fluoxetine-induced plasticity or 'dematuration' causes the cell to revert back to a juvenile state where it is doesn't work as well with other specialized cells. In this study, the authors noted that the behavioral and cellular effects persisted after fluoxetine was discontinued. Dr. Katsunori reported that "the dematuration can be observed 1 month after discontinuation, so it is not readily reversible..."

>> Behavioral destabilization induced by the selective serotonin reuptake> inhibitor fluoxetine> Katsunori Kobayashi, Yumiko Ikeda and Hidenori Suzuki> > *> > > > For all author emails, please log on> <http://www.molecularbrain.com/logon> .> > Molecular Brain 2011, 4:12 doi:10.1186/1756-6606-4-12> Published: 16 March 2011 Abstract (provisional) Background> Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat> mood and anxiety disorders. However, neuronal bases for both beneficial> and adverse effects of SSRIs remain poorly understood. We have recently> shown that the SSRI fluoxetine can reverse the state of maturation of> hippocampal granule cells in adult mice. The granule cell "dematuration"> is induced in a large population of granule cells, and greatly changes> functional and physiological properties of these cells. Here we show> that this unique form of neuronal plasticity is correlated with a> distinct change in behavior of mice.> Results> We chronically treated adult male mice with fluoxetine, and examined its> effect on several forms of behavior of mice. During fluoxetine> treatments, mice showed a marked increase in day-to-day fluctuations of> home cage activity levels that was characterized by occasional switching> between hypoactivity and hyperactivity within a few days. This> destabilized cage activity was accompanied by increased anxiety-related> behaviors and could be observed up to 4 weeks after withdrawal from> fluoxetine. As reported previously, the granule cell dematuration by> fluoxetine includes a reduction of synaptic facilitation at the granule> cell output, mossy fiber, synapse to the juvenile level. Mossy fiber> synaptic facilitation examined electrophysiologically in acute> hippocampal slices also remained suppressed after fluoxetine withdrawal> and significantly correlated with the fluctuation of cage activity> levels in individual mice. Furthermore, in mice lacking the 5-HT4> receptor, in which the granule cell dematuration has been shown to be> attenuated, fluoxetine had no significant effect on the fluctuation of> cage activity levels.> Conclusions> Our results demonstrate that the SSRI fluoxetine can induce marked> day-to-day changes in activity levels of mice in the familiar> environment, and that the dematuration of the hippocampal granule cells> is closely associated with the expression of this destabilized behavior.> Based on these results, we propose that the granule cell dematuration> can be a potential cellular basis underlying switching-like changes in> the behavioral state associated with SSRI treatments.> The complete article is available as a provisional PDF> <http://www.molecularbrain.com/content/pdf/1756-6606-4-12.pdf> . The> fully formatted PDF and HTML versions are in production.>

[Guest guest]

"...They previously showed that fluoxetine could reverse the state of maturation of hippocampal granule cells in adult mice. This fluoxetine-induced plasticity or 'dematuration' causes the cell to revert back to a juvenile state where it is doesn't work as well with other specialized cells. In this study, the authors noted that the behavioral and cellular effects persisted after fluoxetine was discontinued. Dr. Katsunori reported that "the dematuration can be observed 1 month after discontinuation, so it is not readily reversible..."

>> Behavioral destabilization induced by the selective serotonin reuptake> inhibitor fluoxetine> Katsunori Kobayashi, Yumiko Ikeda and Hidenori Suzuki> > *> > > > For all author emails, please log on> <http://www.molecularbrain.com/logon> .> > Molecular Brain 2011, 4:12 doi:10.1186/1756-6606-4-12> Published: 16 March 2011 Abstract (provisional) Background> Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat> mood and anxiety disorders. However, neuronal bases for both beneficial> and adverse effects of SSRIs remain poorly understood. We have recently> shown that the SSRI fluoxetine can reverse the state of maturation of> hippocampal granule cells in adult mice. The granule cell "dematuration"> is induced in a large population of granule cells, and greatly changes> functional and physiological properties of these cells. Here we show> that this unique form of neuronal plasticity is correlated with a> distinct change in behavior of mice.> Results> We chronically treated adult male mice with fluoxetine, and examined its> effect on several forms of behavior of mice. During fluoxetine> treatments, mice showed a marked increase in day-to-day fluctuations of> home cage activity levels that was characterized by occasional switching> between hypoactivity and hyperactivity within a few days. This> destabilized cage activity was accompanied by increased anxiety-related> behaviors and could be observed up to 4 weeks after withdrawal from> fluoxetine. As reported previously, the granule cell dematuration by> fluoxetine includes a reduction of synaptic facilitation at the granule> cell output, mossy fiber, synapse to the juvenile level. Mossy fiber> synaptic facilitation examined electrophysiologically in acute> hippocampal slices also remained suppressed after fluoxetine withdrawal> and significantly correlated with the fluctuation of cage activity> levels in individual mice. Furthermore, in mice lacking the 5-HT4> receptor, in which the granule cell dematuration has been shown to be> attenuated, fluoxetine had no significant effect on the fluctuation of> cage activity levels.> Conclusions> Our results demonstrate that the SSRI fluoxetine can induce marked> day-to-day changes in activity levels of mice in the familiar> environment, and that the dematuration of the hippocampal granule cells> is closely associated with the expression of this destabilized behavior.> Based on these results, we propose that the granule cell dematuration> can be a potential cellular basis underlying switching-like changes in> the behavioral state associated with SSRI treatments.> The complete article is available as a provisional PDF> <http://www.molecularbrain.com/content/pdf/1756-6606-4-12.pdf> . The> fully formatted PDF and HTML versions are in production.>

[Guest guest]

"...They previously showed that fluoxetine could reverse the state of maturation of hippocampal granule cells in adult mice. This fluoxetine-induced plasticity or 'dematuration' causes the cell to revert back to a juvenile state where it is doesn't work as well with other specialized cells. In this study, the authors noted that the behavioral and cellular effects persisted after fluoxetine was discontinued. Dr. Katsunori reported that "the dematuration can be observed 1 month after discontinuation, so it is not readily reversible..."

>> Behavioral destabilization induced by the selective serotonin reuptake> inhibitor fluoxetine> Katsunori Kobayashi, Yumiko Ikeda and Hidenori Suzuki> > *> > > > For all author emails, please log on> <http://www.molecularbrain.com/logon> .> > Molecular Brain 2011, 4:12 doi:10.1186/1756-6606-4-12> Published: 16 March 2011 Abstract (provisional) Background> Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat> mood and anxiety disorders. However, neuronal bases for both beneficial> and adverse effects of SSRIs remain poorly understood. We have recently> shown that the SSRI fluoxetine can reverse the state of maturation of> hippocampal granule cells in adult mice. The granule cell "dematuration"> is induced in a large population of granule cells, and greatly changes> functional and physiological properties of these cells. Here we show> that this unique form of neuronal plasticity is correlated with a> distinct change in behavior of mice.> Results> We chronically treated adult male mice with fluoxetine, and examined its> effect on several forms of behavior of mice. During fluoxetine> treatments, mice showed a marked increase in day-to-day fluctuations of> home cage activity levels that was characterized by occasional switching> between hypoactivity and hyperactivity within a few days. This> destabilized cage activity was accompanied by increased anxiety-related> behaviors and could be observed up to 4 weeks after withdrawal from> fluoxetine. As reported previously, the granule cell dematuration by> fluoxetine includes a reduction of synaptic facilitation at the granule> cell output, mossy fiber, synapse to the juvenile level. Mossy fiber> synaptic facilitation examined electrophysiologically in acute> hippocampal slices also remained suppressed after fluoxetine withdrawal> and significantly correlated with the fluctuation of cage activity> levels in individual mice. Furthermore, in mice lacking the 5-HT4> receptor, in which the granule cell dematuration has been shown to be> attenuated, fluoxetine had no significant effect on the fluctuation of> cage activity levels.> Conclusions> Our results demonstrate that the SSRI fluoxetine can induce marked> day-to-day changes in activity levels of mice in the familiar> environment, and that the dematuration of the hippocampal granule cells> is closely associated with the expression of this destabilized behavior.> Based on these results, we propose that the granule cell dematuration> can be a potential cellular basis underlying switching-like changes in> the behavioral state associated with SSRI treatments.> The complete article is available as a provisional PDF> <http://www.molecularbrain.com/content/pdf/1756-6606-4-12.pdf> . The> fully formatted PDF and HTML versions are in production.>

[Guest guest]

"...They previously showed that fluoxetine could reverse the state of maturation of hippocampal granule cells in adult mice. This fluoxetine-induced plasticity or 'dematuration' causes the cell to revert back to a juvenile state where it is doesn't work as well with other specialized cells. In this study, the authors noted that the behavioral and cellular effects persisted after fluoxetine was discontinued. Dr. Katsunori reported that "the dematuration can be observed 1 month after discontinuation, so it is not readily reversible..."

>> Behavioral destabilization induced by the selective serotonin reuptake> inhibitor fluoxetine> Katsunori Kobayashi, Yumiko Ikeda and Hidenori Suzuki> > *> > > > For all author emails, please log on> <http://www.molecularbrain.com/logon> .> > Molecular Brain 2011, 4:12 doi:10.1186/1756-6606-4-12> Published: 16 March 2011 Abstract (provisional) Background> Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat> mood and anxiety disorders. However, neuronal bases for both beneficial> and adverse effects of SSRIs remain poorly understood. We have recently> shown that the SSRI fluoxetine can reverse the state of maturation of> hippocampal granule cells in adult mice. The granule cell "dematuration"> is induced in a large population of granule cells, and greatly changes> functional and physiological properties of these cells. Here we show> that this unique form of neuronal plasticity is correlated with a> distinct change in behavior of mice.> Results> We chronically treated adult male mice with fluoxetine, and examined its> effect on several forms of behavior of mice. During fluoxetine> treatments, mice showed a marked increase in day-to-day fluctuations of> home cage activity levels that was characterized by occasional switching> between hypoactivity and hyperactivity within a few days. This> destabilized cage activity was accompanied by increased anxiety-related> behaviors and could be observed up to 4 weeks after withdrawal from> fluoxetine. As reported previously, the granule cell dematuration by> fluoxetine includes a reduction of synaptic facilitation at the granule> cell output, mossy fiber, synapse to the juvenile level. Mossy fiber> synaptic facilitation examined electrophysiologically in acute> hippocampal slices also remained suppressed after fluoxetine withdrawal> and significantly correlated with the fluctuation of cage activity> levels in individual mice. Furthermore, in mice lacking the 5-HT4> receptor, in which the granule cell dematuration has been shown to be> attenuated, fluoxetine had no significant effect on the fluctuation of> cage activity levels.> Conclusions> Our results demonstrate that the SSRI fluoxetine can induce marked> day-to-day changes in activity levels of mice in the familiar> environment, and that the dematuration of the hippocampal granule cells> is closely associated with the expression of this destabilized behavior.> Based on these results, we propose that the granule cell dematuration> can be a potential cellular basis underlying switching-like changes in> the behavioral state associated with SSRI treatments.> The complete article is available as a provisional PDF> <http://www.molecularbrain.com/content/pdf/1756-6606-4-12.pdf> . The> fully formatted PDF and HTML versions are in production.>