Abstract
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.