Combined chronic oral methylphenidate and fluoxetine treatment increases CB1 receptor density in the somatosensory forelimb region

Neurosci Lett. 2025 Oct 2:138407. doi: 10.1016/j.neulet.2025.138407. Online ahead of print.

ABSTRACT

Methylphenidate (MP) is a psychostimulant commonly prescribed for attention deficit hyperactivity disorder (ADHD), and Fluoxetine (FLX) is a Serotonin Selective Reuptake Inhibitor (SSRI) commonly prescribed to treat depression and anxiety disorders. Both are shown to impact neurochemistry and behavior, but little is known about their individual and combined impacts on the endocannabinoid system (ECS). We examined the effects of MP and FLX, both as separate treatments and in combination, on cannabinoid receptor type 1 (CB1) binding in several key brain regions of interest. Male rats were treated with either water, MP, FLX, or MP + FLX via a previously established drinking paradigm for three months. Brains were harvested, and [³H] SR141716A in vitro autoradiography was performed to quantify CB1 binding. The combined treatment of MP + FLX showed significantly higher [³H] SR141716A binding compared to the water, MP, and FLX groups in the somatosensory forelimb (S(FL)) region. This indicates an ability of the common co-usage of MP and FLX to increase CB1 levels in the somatosensory cortex: a region of the brain required for the processing of sensory information.

PMID:41046046 | DOI:10.1016/j.neulet.2025.138407