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Antidepressants affect male brains, but do little to female brains: Study

Hindustan Times Mumbai

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July 03, 2025

Antidepressants have a strong impact on male brains—with the nature of the impact depending on the age of the subject—but do not affect female brains, a new study of rats has shown, suggesting that there needs to be more exploration of the physiological effects of such drugs, something that could eventually influence how they are used in treatments.

- Sandhya Ramesh

The neurohormone serotonin plays a large role in shaping emotional pathways in the brain, because of which its regulation is a common target of antidepressants. Selective serotonin reuptake inhibitors (SSRIs) are the most prominent intervention for depression, anxiety, and other neuropsychiatric disorders, and allow for more serotonin in the brain as a result.

Fluoxetine—commonly known by brand names like Prozac, Fludac, and Sarafem—is the most widely used SSRI for all ages, including for pregnant women, lactating mothers, children, and adolescents. The study examines the long-term effects of fluoxetine in rat brains when administered at a young age, leading to a series of findings that raise more questions than answers.

Early administration of the drug led to long-term but wildly opposing changes in male brains—when administered just after birth, the rats became more anxious over time; when administered during the juvenile window when they reach sexual maturity, they developed less anxious and depressive behaviors. Additionally, the researchers also observed changes in neuron structure in the brain, changes to energy production by mitochondria, and gene expressions or activation of a group of genes. Most surprisingly, only male rats were affected by the drug. Female rats that were given the drug at the same time windows displayed no long-term changes in behaviors, brain structure, mitochondria, or genetic expressions.

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