Altered dopaminergic regulation of the dorsal striatum is able to induce tic-like movements in juvenile rats

Abstract

Motor tics are sudden, repetitive, involuntary movements representing the hallmark behaviors of the neurodevelopmental disease Tourette’s syndrome (TS). The primary cause of TS remains unclear. The initial observation that dopaminergic antagonists alleviate tics led to the development of a dopaminergic theory of TS etiology which is supported by post mortem and in vivo studies indicating that non-physiological activation of the striatum could generate tics. The striatum controls movement execution through the balanced activity of dopamine receptor D1 and D2-expressing medium spiny neurons of the direct and indirect pathway, respectively. Different neurotransmitters can activate or repress striatal activity and among them, dopamine plays a major role. In this study we introduced a chronic dopaminergic alteration in juvenile rats, in order to modify the delicate balance between direct and indirect pathway. This manipulation was done in the dorsal striatum, that had been associated with tic-like movements generation in animal models. The results were movements resembling tics, which were categorized and scored according to a newly developed rating scale and were reduced by clonidine and riluzole treatment. Finally, post mortem analyses revealed altered RNA expression of dopaminergic receptors D1 and D2, suggesting an imbalanced dopaminergic regulation of medium spiny neuron activity as being causally related to the observed phenotype.

Level of Insight in Patients With Obsessive–Compulsive Disorder: An Exploratory Comparative Study Between Patients With “Good Insight” and “Poor Insight”

“…As the CTOC sample is predominantly composed of specialized and tertiary health services, the recruitment of more severe patients, nonresponders to conventional and complex treatments (with comorbidities with tics, for example), may have biased our results, leading to a greater prevalence of the use of these specific medications in these centers (39, 42, 85). As poor insight was related to sensory phenomena, and since sensory phenomena are more prevalent in patients with OCD who also have tics (64, 86), we could speculate a “dopaminergic” modulation of “poor insight.” It could be explained by the facts that tics occur due to dopaminergic dysfunctions involving the basal nuclei, especially striatum and substantia nigra (87, 88), which may result clinically in the increased prescription of drugs with dopaminergic action, such as neuroleptics. Thus, the association of an atypical neuroleptic with SSRIs could act, in these cases, with synergism by serotonergic potentiation or with synergism by addition, adding effect in the involved dopaminergic neurocircuits.…”

Introducing Precision Addiction Management of Reward Deficiency Syndrome, the Construct That Underpins All Addictive Behaviors

“…To date, there have been 150 articles in PUBMED, and the SAGE Encyclopedia of Abnormal and Clinical Psychology published a definition in 2017 ( 8 ). The RDS concept arose from the findings that dysfunction in the dopaminergic system are implicated in reward mechanisms in the brain and lead to substance seeking behavior and non-substance addictive behaviors ( 7 ) like pathological gambling ( 9 – 11 ), Tic Disorders ( 12 , 13 ), Tourette's syndrome ( 14 ), and attention deficit hyperactivity disorder (ADHD) ( 15 – 17 ).…”

Effects of Acupuncture on Behavioral Stereotypies and Brain Dopamine System in Mice as a Model of Tourette Syndrome

“…Dopamine (DA) is a neurotransmitter that can regulate neural processes including motor control, cognition, and memory (Chun et al, 2013). Previous studies have suggested that the imbalanced expression of DA plays an important role in the development of TS (Nespoli et al, 2018).…”