<p>This study (a) used the forced swim test in a rat model of Parkinson’s disease (PD) to characterise the antidepressant-like effect of hydroxytyrosol (Hty) against 1-methyl-4-phenylpyridinium (MPP⁺) and (b), studied dopamine and serotonin levels in the striatum. Rats were intravenously administered 1.5&#xa0;mg/kg Hty via the tail vein 5&#xa0;min before an intra-striatal infusion of 10&#xa0;µg MPP⁺; control animals received saline. After 6 days, locomotor activity was assessed in an open-field test and antidepressant-like effects were tested using the forced swim test. On day 6, all the animals received apomorphine (1&#xa0;mg/kg, s.c.) and ipsilateral rotations were recorded for an hour before sacrifice and removal of striatal tissues for dopamine and serotonin quantification. Neither MPP⁺ injection nor Hty altered locomotor activity. Hty pretreatment significantly reduced immobility time, increased climbing time in the forced swim test, and diminished the number of ipsilateral rotations induced by apomorphine in rats treated with MPP⁺. These effects were consistent with an increase in dopamine and serotonin levels. These results show that Hty had antidepressant-like activity in the forced swim test in the rat MPP⁺ model and protected against MPP⁺ neurotoxicity, suggesting its potential utility in the treatment of neurodegenerative diseases such as PD and depression.</p>