Trihexyphenidyl has a psychostimulant-like effect on mice

Trihexyphenidyl is an antimuscarinic agent used for managing motor symptoms in Parkinson’s disease (PD). Despite its therapeutic use, trihexyphenidyl misuse and addiction have been reported. Its antimus¬carinic effect alone does not explain this abuse potential. This study investigated if trihexyphenidyl pro¬duces psychostimulant-like behavioural effects in mice related to dopamine signalling. Male and female mice received 1 or 2 mg/kg trihexyphenidyl orally before open field and forced swim tests. Trihex¬yphenidyl at 2 mg/kg increased locomotor activity, prevented by olanzapine pre-treatment. It also de¬creased forced swim test immobility time. These findings suggest trihexyphenidyl has dopamine-medi¬ated psycho-stimulant properties, providing preclinical evidence for its abuse liability. Further studies on trihexyphenidyl’s impact on dopamine neurotransmission and addiction risk are warranted.