Anxiety-like behavior induced by 6-OHDA animal model of Parkinson’s disease may be related to a dysregulation of neurotransmitter systems in brain areas related to anxiety

The Noradrenergic System in Parkinson’s Disease

“…Similarly, other areas with sparse noradrenergic innervation, as the striatum, show unchanged or lower NA levels (Shin et al, 2014;Ostock et al, 2018). Bilateral models of 6-OHDA show, however, more robust NA deficits in the cortex and striatum (Vieira et al, 2019). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys exhibit clear noradrenergic damage, including LC cell loss, lower NA concentrations in several brain regions, and reduced noradrenergic innervation of the SNc and the subthalamic nucleus (Pifl et al, 1991;Masilamoni et al, 2017).…”

“…At the behavioral level, regardless inconsistencies found through the scientific publications, p a r k i n s o n i a n a n i m a l s t e n d t o m i m i c t h e h u m a n symptomatology showing motor but also non-motor impairments (Titova et al, 2017). An array of studies report that rodents lesioned with 6-OHDA or MPTP show anxious and depressive behavior, pain, cognitive, and sleep disturbances (Monaca et al, 2004;Pérez et al, 2009;Berghauzen-Maciejewska et al, 2014;Vo et al, 2014;Kamińska et al, 2017;Charles et al, 2018;Campos et al, 2019;Domenici et al, 2019), more notably in bilateral models of the disease (Ferro et al, 2005;Tadaiesky et al, 2008;Santiago et al, 2010;Bonito-Oliva et al, 2014;Vieira et al, 2019). Although the participation of other nuclei cannot be ruled out, the role of the LC in the mentioned functions is widely accepted.…”

Dopamine neurons in the ventral periaqueductal gray modulate isoflurane anesthesia in rats

“…The neurotoxin 6-OHDA is commonly used to selectively destroy dopaminergic neurons and is therefore often used to establish Parkinson's disease models. 18 The rats in the sham group (n = 10) were injected with 1 μL saline into the vPAG using the same procedure. All rats were allowed two weeks to recover before subsequent experiments.…”

“…Brain slices were constantly perfused with artificial cerebrospinal fluid (ACSF) saturated with 95% O 2 and 5% CO 2 at room temperature. The vPAG neurons were visually identified using a BX51WI microscope (Olympus) equipped with infrared-differential interference contrast optics, as described previously (18)…”

“…The effective concentration of 1.4% isoflurane dissolved in ACSF is 0.50 mmol/L. 18 Other drugs dissolved in ACSF were perfused using a BPS-4 perfusion system (ALA, USA). We started to record the current after 10 minutes of drug application, and the recording time was 5 minutes.…”