A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

Abstract

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug.

An Invasive Method for the Activation of the Mouse Dentate Gyrus by High-frequency Stimulation

“…General limitations of HF-DBS have been extensively reviewed elsewhere 24,25 . One of the challenges for the experiment here is also the need for an excellent surgical technique and for the ongoing care of surgical anatomical locus.…”

Development of a Non-invasive Deep Brain Stimulator With Precise Positioning and Real-Time Monitoring of Bioimpedance

“…As a typical neurosurgical procedure, DBS has been used to cure abnormal neuronal firing patterns that result from certain diseases, such as Parkinson's disease, essential tremors, and dystonia (Flora et al, 2010 ; Miocinovic et al, 2013 ). However, careful wound care and personal hygiene are needed to protect DBS hardware and to avoid additional negative impacts after the surgery (Umemura et al, 2003 ; Blomstedt and Hariz, 2006 ; Batra et al, 2016 ). Studies on non-invasive brain stimulation that does not require built-in hardware are accumulating rapidly.…”

Intermittent bilateral deep brain stimulation of the nucleus accumbens shell reduces intravenous methamphetamine intake and seeking in Wistar rats

“…Previous experiments indicated that this initial prolonged and "easy" access results in the majority of rodents acquiring significant drug-taking behavior in less than 1 week. 3 During the 2nd and 3rd weeks of training, rats underwent 2-hour daily sessions at approximately the same time Monday through Friday, again on an FR1 schedule of reinforcement culminating in the rats developing a baseline intake termed "maintenance." Maintenance was operationally defined as stable, intense responding for which the total number of methamphetamine infusions across each session varied less than approximately 10% for 3 consecutive sessions and the cumulative number of infusions across the 1st 30 minutes was greater than, or equal to, the cumulative number of infusions during the 2nd 30 minutes.…”

“…This criterion ensured that the rats developed a drug-loading pattern that indicated addictive behavior 1 and not simply casual use by the time treatment was initiated. 3 Once maintenance had been established, rats were counterbalanced based on total baseline 2-hour IV methamphetamine infusions and divided in 2 groups, active stimulation (DBS) and sham stimulation (sham).…”