Will Electrical Brain Stimulation Technology Aid in Treating Substance Use Disorders?

Abuse of intoxicants causes neuroadaptive changes and consequent behavior is mediated by synaptic plasticity of catecholamine receptors, primarily dopamine (DA) in the nucleus accumbens (NAc). Psychoactive substances activate dopamine circuitry in the midbrain, via the Ventral Tegmental Area, NAc, and then on to the Medial Prefrontal Cortex (mPFC). Repeated drug exposure produces a “memory trace” in the reward system by increasing levels of central dopamine in the aforementioned areas. This is a result of micro-evolutionary driven survival drives in the primitive midbrain and the rational prefrontal areas. Not unlike the process that allowed our ancestors to “remember” where to hunt, gather food, and find clean water, the dopaminergic reward system can remember where to find drugs or how to attain the currency for them. This is what is meant by “hijacking” the brain. Drugs of abuse fool the brain by providing “salience” meant for survival behaviors that become co-opted into providing salience for drug seeking and drug taking behavior.

In her recent essay in the journal Science, Meghan Creed, PhD, asserts that synaptic plasticity from substance abuse is not exhibited acutely in the reward system during or immediately following intoxication. Rather, it persists during periods of abstinence. This, she emphasizes, explains much of the adaptive behaviors observed in addicts—such as craving, drug seeking and anhedonia during abstinence. Animal models clearly demonstrate that dopamine expression (D1 or D2 receptors) integrate excitatory inputs from the medial prefrontal cortex (PFC) and receive dopaminergic projections from the ventral tegmental area (VTA). These functional deficits are stubborn, as are all survival behaviors. Why? Because the cost of failure is too high.

To date, pharmacological interventions to stabilize the reward system and reduce neuroadaptive behaviors are mediated by numerous somatic and metabolic variants, which make targeting specific brain areas and functions very difficult.

Electrical Brain Stimulation

Electrical Convulsive Therapy (ECT), Deep Brain Stimulation (DBS) and Transcranial Magnetic Stimulation (TMS) are among the non-pharmacological treatments that are FDA-approved for various neurological and psychiatric pathology such as Parkinson’s Disease, intractable and treatment resistant depression (TRD). Because the effects are transient, practical clinical applications are complicated, costly, confusing, time consuming and inconvenient. But the efficacy for specific conditions are excellent.

As addictive disease has been grabbing more and more headlines, additional research is being funded (not nearly enough) to investigate some novel but potentially beneficial non-pharmacological treatments.

Optogenetic therapy is neuromodulation that combines techniques from optics and other neuromodulation procedures such as DBS to modify neural activity patterns. Optogenetic methods have greatly advanced our understanding of the function of specific neural circuitry. Because we understand the neuronal circuitry involved in addiction, refining a procedure that activates mGluRs, could reduce the excitatory synaptic inputs from binding with dopamine D1 receptor medium-sized spiny neurons (D1-MSNs), and normalizes drug-adaptive behavior.

For this reason, Creed and colleagues employed optogenetic principles and a novel procedure to reverse the neuroadaptive behavioral patterns in cocaine-addicted rodents. Creed discovered that administering low-frequency DBS, combined with blocking selective D1 receptors, mimicked mGluRs, which resulted in the normalization of neurotransmission.

Translating these findings to the next level, perhaps primates would allow observation and measurement of craving, emotional response and drug seeking behavior. But that is a huge experimental leap—but given the current epidemic and mortality, it is one worth taking.