A single intranigral administration of β-sitosterol β-d-glucoside elicits bilateral sensorimotor and non-motor alterations in the rat

A single intranigral administration of BSSG induces non-motor alterations such as hyposmia and depressive-like behavior as well as motor alterations such as decreased locomotor activity and postural instability. These bilateral sensorimotor impairments could be associated with a decrease in the number of mesencephalic dopaminergic neurons and by Lewy body-like synuclein aggregates and cause a dysfunction in the nigrostriatal (orange lines) and mesolimbic pathways (yellow lines), and in the direct connection (orange line) between the substantia nigra pars compacta (SNpc) and the olfactory bulb (OB). VTA = ventral tegmental area; A = amygdala; NA = nucleus accumbens; PFC = prefrontal cortex; OFC = orbitofrontal cortex. [Display omitted] •A Parkinson’s disease rat model is described using BSSG.•Intranigral BSSG administration induces depressive-like behavior and hyposmia.•Intranigral BSSG administration decreases locomotor activity in the rat.•Unilateral BSSG administration causes bilateral loss of dopaminergic mesencephalic neurons. Parkinson's disease (PD) is a progressive neuropathology characterized by motor and non-motor alterations. β-sitosterol β-d-glucoside (BSSG) is a neurotoxin whose prolonged oral administration in rats has been proposed as a new PD model. Herein, we demonstrate that a single, unilateral, and intranigral administration of BSSG also elicits bilateral sensorimotor alterations in the rat. Six behavioral tests evaluated the effect of different concentrations of BSSG (3, 6, 9, and 12 μg/μL DMSO) from 15 to 120 days after administration. The first behavioral alterations, which appeared on day 15, were unbalanced and uncoordinated gaits and a decrease in the sensorimotor cortex activity, as evidenced by the beam-walking and the vibrissae tests, respectively. After 30 days, the corridor test revealed hyposmia and a decreased locomotor activity in the open field. The last alteration was a depressive-like behavior, as shown by the forced swim test on days 60 and 120. According to the cylinder test, no locomotor asymmetry was observed over time with any BSSG concentrations tested. Also, a mesencephalic TH(+) cell loss (p