Ranitidine

BALB/c mice were injected with cysteamine HCl every other day for three days to induce duodenal ulceration and increase systemic histamine. Following this treatment period, half of the mice were administered Ranitidine in their drinking water for the subsequent 14 days. Control, cysteamine-only, Ranitidine-only and combined-treatment groups were compared in an open-field test, a light-dark box and elevated-plus-maze.
Cysteamine alone caused a reduction in locomotion, an increase in thigmotaxis, an increase in time spent in the dark compartment and closed arms, and a reduction in exploration of open areas, confirming the presence of a pronounced anxiety phenotype. The co-administration of Ranitidine reversed each of these deficits, and restored levels of exploration to or above that of the control animals. Histologically, cysteamine treatment reduced the number of CA3 pyramidal cells, and increased the number of activated, hypertrophic, or amoeboid microglia. In contrast, Ranitidine increased the neuronal density and shifted microglia towards a resting, ramified morphology. The Ranitidine-alone animals had even higher numbers of neurons and the lowest levels of microgliosis. The authors suggest that during GI injury, excessive amounts of histamine are released and bind to H₂ receptors on microglia, which leads to neuro-inflammation that damages CA3 neurons and leads to an anxious phenotype. By blocking both peripheral and central H₂ receptors, Ranitidine is able to attenuate this neuro-immune cascade, which has neuroprotective and anti-inflammatory effects, and ultimately leads to anxiolysis.

Fig. 1 Ranitidine relieves anxiety-like behaviors linked to gastrointestinal disorders. (Selvaraj D B.; et al. 2023)