Washington, May 28 (ANI): Using a new experimental mouse model of depression/anxiety, scientists have found that the anti-depressant effects of drugs like Prozac involve both neurogenesis-dependent and -independent mechanisms.
The finding could lead to development of better treatments for depression and anxiety.
The mouse model is the first to permit simultaneous examination of multiple effects of antidepressant treatment in the same animal.
Not much is known about the specific molecular influences of selective serotonin reuptake inhibitors (SSRIs) and other types of antidepressants commonly prescribed for treatment of depression and anxiety disorders.
"Recently, compelling work in rodents has suggested that SSRIs may stimulate changes in a brain region called the hippocampus as well as other brain structures. For example, anxiety/depression-like changes in behavior have been linked with a decrease in cell proliferation in the hippocampus, a change that is reversed by antidepressants," said study author Dr. Denis J. David from the University of Paris-Sud.
Previous studies have already confirmed that long-term exposure to glucocorticoids induces anxiety and a depressive-like state in rodents. Elevated glucocorticoid levels have been linked with depression and anxiety in humans.
"We developed an anxiety/depression-like model based on elevation of glucocorticoid levels that offered an easy and reliable alternative to existing models," said David.
Chronic anti-depressant treatment reversed the behavioural dysfunctions and inhibition of hippocampal neurogenesis observed in the experimental mice.
They observed that when hippocampal neurogenesis was prevented, the efficacy of Prozac was blocked in some but not all of the behavioural paradigms.
The researchers could identify candidate genes whose expression was decreased in a brain region called the hypothalamus and normalized by Prozac.
Mice deficient in one of these genes, beta-arrestin 2, displayed a reduced response to Prozac in multiple behavioural tasks.
This indicated that beta-arrestin signalling is necessary for the antidepressant effects of Prozac.
The finding suggested that both neurogenesis-dependent and - independent mechanisms underlie antidepressant actions.
The study has been published in the latest issue of the journal Neuron. (ANI)
The finding could lead to development of better treatments for depression and anxiety.
The mouse model is the first to permit simultaneous examination of multiple effects of antidepressant treatment in the same animal.
Not much is known about the specific molecular influences of selective serotonin reuptake inhibitors (SSRIs) and other types of antidepressants commonly prescribed for treatment of depression and anxiety disorders.
"Recently, compelling work in rodents has suggested that SSRIs may stimulate changes in a brain region called the hippocampus as well as other brain structures. For example, anxiety/depression-like changes in behavior have been linked with a decrease in cell proliferation in the hippocampus, a change that is reversed by antidepressants," said study author Dr. Denis J. David from the University of Paris-Sud.
Previous studies have already confirmed that long-term exposure to glucocorticoids induces anxiety and a depressive-like state in rodents. Elevated glucocorticoid levels have been linked with depression and anxiety in humans.
"We developed an anxiety/depression-like model based on elevation of glucocorticoid levels that offered an easy and reliable alternative to existing models," said David.
Chronic anti-depressant treatment reversed the behavioural dysfunctions and inhibition of hippocampal neurogenesis observed in the experimental mice.
They observed that when hippocampal neurogenesis was prevented, the efficacy of Prozac was blocked in some but not all of the behavioural paradigms.
The researchers could identify candidate genes whose expression was decreased in a brain region called the hypothalamus and normalized by Prozac.
Mice deficient in one of these genes, beta-arrestin 2, displayed a reduced response to Prozac in multiple behavioural tasks.
This indicated that beta-arrestin signalling is necessary for the antidepressant effects of Prozac.
The finding suggested that both neurogenesis-dependent and - independent mechanisms underlie antidepressant actions.
The study has been published in the latest issue of the journal Neuron. (ANI)
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