Background: Opioid dependence and death in America have reached epidemic proportions.
Since 2000, we have seen an increase of over 3,000 percent in patients seeking treatment for
substance use disorders. The “gold standard” for medically –assisted treatment, that is, Buprenorphine
(a partial opioid agonist), combined with Naloxone, an opioid antagonist. Unfortunately, the
relapse rates for Buprenorphine programs are high, and withdrawal reactions are common when
Buprenorphine is precipitously discontinued. We must find approaches to treating substance use
disorders that are more effective.
Objectives: This report reviews the neuropharmacology of neurotransmitters involved in brain reward
circuitry to increase understanding of the effect of Buprenorphine/Naloxone treatment on patients
with substance use disorders.
Discussion: We provide evidence, from animal and human models, regarding the acute and chronic
effects of Buprenorphine on Dopaminergic reward processing. Microdialysis in animal models reveals
that acute Buprenorphine tends to increase mesolimbic dopamine release. However, longterm
use tends to decrease dopamine release. Cessation of Buprenorphine combination treatment
increases drug reinstatement and relapse.
Conclusions: This review of both the acute and chronic effects of Buprenorphine naloxone combination
therapy on neurotransmission and behavior suggests new treatment targets and clinical options.
“Pro-Dopamine Regulation” to induce dopaminergic homeostasis, via new options, other than
the current, underutilized FDA approved Medication Assisted Treatments, which favor dopamine
antagonism is proposed. We hypothesize that dopamine homeostasis is a crucial process that suppresses
withdrawal symptoms, drug seeking and relapse in abstinent individuals.