Effect of acute trihexyphenidyl abuse on rat motor area of cerebral cortex: light and electron microscopic study

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Trihexyphenidyl (THP) is an antiparkinsonian drug, most frequently abused to achieve pleasurable effects. In contrast, the effect of THP abuse on the motor area of the frontal cortex has not been adequately investigated.

Aim of the work

To study the histological changes of different single doses of TPH on rat motor area.

Materials and methods

Forty-eight adult male rats were used in this study. The rats were divided equally into four groups: a control group (group I), and three experimental groups (groups II, III, and IV) which were intraperitoneally injected with a single variable dose of TPH (0.2, 0.5, 1.0 mg/kg/body weight, respectively). After 6 h of injection, blood samples were collected for measurement of serum THP level. Specimens from the frontal cortex motor area were taken, processed, and examined by light and electron microscopes.


By microscopic examination, the motor area of group II rat which received a TPH dose equivalent to the human therapeutic dose was nearly similar to that of the control. In group III, TPH induced apoptotic changes in the pyramidal and granular cells. Some pyramidal cells exhibited ultrastructural changes including; dilated Golgi saccules, dilated rough endoplasmic reticulum cisternae, multiple lysosomes, and cristolysis of the mitochondria. Moreover, the axons exhibited axoplasmic vacuoles and multiple splitting of the myelin lamellae. Group IV motor areas, showed multiple apoptotic cells and focal necrotic areas with microglial infiltration. Electron microscopic study revealed degenerated pyramidal cells and extravasation of red blood corpuscles. The axons showed multiple focal losses of the myelin lamellae.


TPH induced dose-dependent structural changes in rat frontal cortex motor area. Therefore, THP prescription must be under strict supervision.

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