This week’s Neury Thursday is a challenge to write because it features a fabulously comprehensive research study using methodologies that I’m still, as a novice, struggling to understand (Wikipedia isn’t much help); San Franciscan researchers utilized optogenetics, the combination of genetic (i.e. knock-outs) and channelrhodopsin to elucidate co-expressing dopaminergic and glutamatergic brain centers implicated with drug reward. The regulation of drug (or any type) addiction is currently a heated area of investigation (even in my lab…see circadian regulation of mood disorders ), but though many labs are employing neurobehavioral and pharmacological paradigms to study this type of regulation, we can’t ignore cellular regulation, and therefore, need to exploit the fabulous molecular techniques widely available.

ResearchBlogging.orgI present the paper here because I don’t feel confident explaining the exact methodological details without any misinterpretation and/or overassumption. But I will tell you that through the utility of channelrhodopsin, conditional gene knock-outs (knocking-out a gene within a particular structure and not holistically), and selective receptor antagonism, it was found that neuronal terminals in the nucleus accumbens (mecca center of drug reward) and not the dorsal striatum co-release dopamine and glutamate.

As the neurobehaviorist, I wonder what’s the big picture? Obviously, it’s additional evidence that dopamine and glutamate dually interact to control alterations in the neurochemical environment associated with a drug challenge. As a graduate student “expert” in the neurobiology of alcoholism, it’s well known that alcohol (both binge-drinking and long-term consumption) causes hyperglutamatergic and dopaminergic states. Until recently, these two alcohol-induced neurochemical phenomena were postulated to arise separately, not concomitantly. Though this information may initially frustrate pharmaceutical chemists attempting to make a drug that acts on co-glutamate/dopamine releasing sites in the brain, this dual pharmacological mediatior will hopefully be more efficacious than the extremely selective drugs (with respect to neuromodulatory pathways) currently available for drug addiction (i.e. Campral, an alcohol relapse drug, antagonizes glutamatergic neuromodulatory systems; Naltrexone, a universal relapse drug, antagonizes opiodergic systems).

Stuber, G., Hnasko, T., Britt, J., Edwards, R., & Bonci, A. (2010). Dopaminergic Terminals in the Nucleus Accumbens But Not the Dorsal Striatum Corelease Glutamate Journal of Neuroscience, 30 (24), 8229-8233 DOI: 10.1523/JNEUROSCI.1754-10.2010