Contribution of Decreased Serotonin Release to the Antidyskinetic Effects of Deep Brain Stimulation in a Rodent Model of Tardive Dyskinesia: Comparison of the Subthalamic and Entopeduncular Nuclei

Abstract

Mechanisms whereby deep brain stimulation (DBS) of the subthalamic nucleus (STN) or internal globus pallidus (GPi

Role for the nicotinic cholinergic system in movement disorders; therapeutic implications

“…These data provide proof-of-principle that nicotine exerts its effect via an interaction at nAChRs. Varenicline reduced VCMs to a greater extent than nicotine, a finding that may relate to varenicline’s ability to interact with 5-HT receptors (Creed-Carson, Oraha, & Nobrega, 2011; Creed, Hamani, Bridgman, Fletcher, & Nobrega, 2012; Lummis, Thompson, Bencherif, & Lester, 2011; Naidu & Kulkarni, 2001). …”

Cellular, molecular, and clinical mechanisms of action of deep brain stimulation—a systematic review on established indications and outlook on future developments

“…Recently, renewed appreciation of serotonin's role in the motor and non‐motor symptoms of PD has stimulated research into the serotonergic effects of DBS treatment for movement disorders. In a haloperidol‐induced tardive dyskinesia rat model, STN‐DBS resulted in reduced serotonin release from the dorsolateral striatum, correlating with reduced dyskinetic movements in the animals (Creed et al , ). However, the same experiment found that when serotonin reduction is pharmacologically blocked, STN‐DBS was still able to rescue the phenotype, suggesting that several parallel therapeutic mechanisms are involved (Creed et al , ).…”

The mechanisms of action of deep brain stimulation and ideas for the future development

“…Treatment of hypokinetic disorder such as PD with 1220 STN-DBS may act by increase in GABA levels in the STN and 1221 thereby reduce the GABAergic GPi output to thalamus and 1222 strengthening thalamocortical facilitation, producing the clinical benefits (Feuerstein et al, 2011 GABA in the STN while the PD patients performed a memory task 1233 during surgery (Buchanan et al, 2014). Also, a study in 6-OHDA 1234 model of PD in mice (Yoon et al, 2014) (Creed 1260(Creed et al, 2012. Mood and cognition are also important non-motor 1261 features of PD (Emre et al, 2014).…”

“…Mood and cognition are also important non-motor 1261 features of PD (Emre et al, 2014). In a rat model of tardive 1262 dyskinesia (Creed et al, 2012), STN-DBS decreased the activity of 1263 raphe neurons and thereby reduced serotonin levels, which 1264 produced the antidyskinetic effects. This decrease in serotonin 1265 levels has also been proposed as mechanism of depression in PD 1266 patients treated with STN-DBS (Creed et al, 2013) and GPi-DBS 1267 yielded a lower rate of depression than STN-DBS (Rodriguez-Oroz 1268.…”

“…Furthermore, in an animal model of depression, 1277 stimulation of ventromedial prefrontal cortex modulated the 1278 serotonergic system (Hamani et al, 2012) and this target has been 1279 used in the treatment of depression. Hence, stimulation targets 1280 modulating serotonergic dorsal raphe neurons increasing levels of 1281 serotonin are promising methods to improve depression, which is 1282 a common non-motor symptom in PD.…”