Posts tagged fluoxetine
Articles and news from the latest research reports.
Antidepressant drug induces a juvenile-like state in neurons of the prefrontal cortex
For long, brain development and maturation has been thought to be a one-way process, in which plasticity diminishes with age. The possibility that the adult brain can revert to a younger state and regain plasticity has not been considered, often. In a paper appearing on November 4 in the online open-access journal Molecular Brain, Dr. Tsuyoshi Miyakawa and his colleagues from Fujita Health University show that chronic administration of one of the most widely used antidepressants fluoxetine (FLX, which is also known by trade names like Prozac, Sarafem, and Fontex and is a selective serotonin reuptake inhibitor) can induce a juvenile-like state in specific types of neurons in the prefrontal cortex of adult mice.
In their study, FLX-treated adult mice showed reduced expression of parvalbumin and perineuronal nets, which are molecular markers for maturation and are expressed in a certain group of mature neurons in adults, and increased expression of an immature marker, which typically appears in developing juvenile brains, in the prefrontal cortex. These findings suggest the possibility that certain types of adult neurons in the prefrontal cortex can partially regain a youth-like state; the authors termed this as induced-youth or iYouth. These researchers as well as other groups had previously reported similar effects of FLX in the hippocampal dentate gyrus, basolateral amygdala, and visual cortex, which were associated with increased neural plasticity in certain types of neurons. This study is the first to report on “iYouth” in the prefrontal cortex, which is the brain region critically involved in functions such as working memory, decision-making, personality expression, and social behavior, as well as in psychiatric disorders related to deficits in these functions.
Network dysfunction in the prefrontal cortex and limbic system, including the hippocampus and amygdala, is known to be involved in the pathophysiology of depressive disorders. Reversion to a youth-like state may mediate some of the therapeutic effects of FLX by restoring neural plasticity in these regions. On the other hand, some non-preferable aspects of FLX-induced pseudo-youth may play a role in certain behavioral effects associated with FLX treatment, such as aggression, violence, and psychosis, which have recently received attention as adverse effects of FLX. Interestingly, expression of the same molecular markers of maturation, as discussed in this study, has been reported to be decreased in the prefrontal cortex of postmortem brains of patients with schizophrenia. This raises the possibility that some of FLX’s adverse effects may be attributable to iYouth in the same type of neurons in this region. Currently, basic knowledge on this is lacking, and there are several unanswered questions like: What are the molecular and cellular mechanisms underlying iYouth? What are the differences between actual youth and iYouth? Is iYouth good or bad? Future studies to answer these questions could potentially revolutionize the prevention and/or treatment of various neuropsychiatric disorders and aid in improving the quality of life for an aging population.
(Source: eurekalert.org)
Induction of adult cortical neurogenesis by an antidepressant
The production of new neurons in the adult normal cortex in response to the antidepressant, fluoxetine, is reported in a study published online this week in Neuropsychopharmacology.
The research team, which is based at the Institute for Comprehensive Medical Science, Fujita Health University, Aichi, has previously demonstrated that neural progenitor cells exist at the surface of the adult cortex, and, moreover, that ischemia enhances the generation of new inhibitory neurons from these neural progenitor cells. These cells were accordingly named “Layer 1 Inhibitory Neuron Progenitor cells” (L1-INP). However, until now it was not known whether L1-INP-related neurogenesis could be induced in the normal adult cortex.
Tsuyoshi Miyakawa, Koji Ohira, and their colleagues employed fluoxetine, a selective serotonin reuptake inhibitor, and one of the most widely used antidepressants, to stimulate the production of new neurons from L1-INP cells. A large percentage of these newly generated neurons were inhibitory GABAergic interneurons, and their generation coincided with a reduction in apoptotic cell death following ischemia. This finding highlights the potential neuroprotective response induced by this antidepressant drug. It also lends further support to the postulation that induction of adult neurogenesis in cortex is a relevant prevention/treatment option for neurodegenerative diseases and psychiatric disorders.
(Source: eurekalert.org)
Fluoxetine increases aggressive behavior, affects brain development among adolescent hamsters
Fluoxetine was the first drug approved by the FDA for major depressive disorder (MDD) in children and adolescents, and to this date, it remains one of only two selective serotonin reuptake inhibitors (SSRIs) registered for treatment of MDD in children and adolescents, despite reports that indicate this class of drugs is associated with side effects, such as agitation, hostility and aggression.
SSRIs have been amongst the most widely prescribed medications in psychiatry for over a decade. While there is a wealth of information regarding their effectiveness and safety in adults, considerably less data exists regarding whether they are safe for children.
A study published in Behavioral Neuroscience by Prof. Richard Melloni of Northeastern University shows that repeated administration of a low dose of fluoxetine to adolescent hamsters dramatically increased offensive aggression and altered the development of brain areas directly associated with controlling the aggressive response. “These data show clearly that repeated exposure to fluoxetine during adolescence directly stimulates aggressive responding and alters the normal development of two important brain systems, i.e., the serotonin and vasopressin neural systems, in a fashion consistent with the expression of the highly aggressive behavioral characteristics.”
For over a decade, Prof. Melloni and his team have researched the neural and behavioral consequences of illicit drugs and prescribed medications on the adolescent brain. Importantly, the data collected during the study indicates that clinically relevant doses of fluoxetine, when administered during adolescent development, can dramatically alter the wiring of brain circuits implicated in aggression control. “These data support the notion that interactions between adolescent fluoxetine and the developing vasopressin neural system might underlie fluoxetine-induced aggressive behavior and hint that serotonin, perhaps by acting on vasopressin neurons, may play a more permissive role in this response.”
(Image credit: Benjah-bmm27)
(Source: northeastern.edu)