Distinguished Seminars in Neuroscience and Pharmacology

 

Department of Neuroscience and Pharmacology, University of Copenhagen

Faculty Club

May 22, 2014

   

Nora D. Volkow

Advances in addiction research

 

 

 

 

 

Nora Volkow has for the last 10 years been director of the National Institute of Drug Abuse (NIDA), NIH, Bethesda

 

 

 

 
Nora Volkow has been amazingly productive and successful in several areas of research, most of it involving dopamine and neuroimaging. Her lecture dealt with changes in DA systems in addiction.    

Volkow, N. D., Wang, G. J., Tomasi, D., & Baler, R. D. (2013). Unbalanced neuronal circuits in addiction. Current Opinion in Neurobiology, 23, 639-648.
Through sequential waves of drug-induced neurochemical stimulation, addiction co-opts the brain's neuronal circuits that mediate reward, motivation to behavioral inflexibility and a severe disruption of self-control and compulsive drug intake. Brain imaging technologies have allowed neuroscientists to map out the neural landscape of addiction in the human brain and to understand how drugs modify it
 

Volkow, N. D., Wang, G. J., Fowler, J. S., Tomasi, D., & Telang, F. (2011). Addiction: beyond dopamine reward circuitry. Proceedings of the National Academy of Sciences of the United States of America, 108, 15037-15042.
Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction is much less clear. This review focuses on studies that used PET to characterize the brain DA system in addicted subjects. These studies have corroborated in humans the relevance of drug-induced fast DA increases in striatum [including nucleus accumbens (NAc)] in their rewarding effects but have unexpectedly shown that in addicted subjects, drug-induced DA increases (as well as their subjective reinforcing effects) are markedly blunted compared with controls. In contrast, addicted subjects show significant DA increases in striatum in response to drug-conditioned cues that are associated with self-reports of drug craving and appear to be of a greater magnitude than the DA responses to the drug. We postulate that the discrepancy between the expectation for the drug effects (conditioned responses) and the blunted pharmacological effects maintains drug taking in an attempt to achieve the expected reward. Also, whether tested during early or protracted withdrawal, addicted subjects show lower levels of D2 receptors in striatum (including NAc), which are associated with decreases in baseline activity in frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (anterior cingulate gyrus), whose disruption results in compulsivity and impulsivity. These results point to an imbalance between dopaminergic circuits that underlie reward and conditioning and those that underlie executive function (emotional control and decision making), which we postulate contributes to the compulsive drug use and loss of control in addiction

 
     

 

Discussion


Anders Fink-Jensen

is one of our local experts on addiciton

He wrote the chapter on cocaine in HjerneForum's book on addiction in 2007

 
     
In HjerneForums book I (AG) also wrote about my understanding of motivation, reward and addiction: Gade, A. (2007). Motivation, belønning og afhængighed. I J.Bøgeskov & K. Ellemann (Eds.), Den afhængige hjerne (pp. 5-31). København: HjerneForum. I concentrated mainly on the dopaminergic reward system, the frontostriatal loops, and on the learning mechanisms in the transition from ventral to dorsal striatum involved in habit learning. It was not wrong, but it was simplistic  compared to current understanding.    

According to Nora Volkow, addiction leads to neuroadaptations in many different brain mechanisms, involving different aspects of dopamine. These may profitably be viewed as three brain circuitries, involved in reward,  withdrawal negative affect, and craving and compromised control, respectively.

Nora Volkow's contributions to the understanding of loss of control in addiction is well summarized in the Nature Reviews in Neuroscience paper below.

 
 
Goldstein, R. Z. & Volkow, N. D. (2011). Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications. Nature Reviews Neuroscience, 12, 652-669.
The loss of control over drug intake that occurs in addiction was initially believed to result from disruption of subcortical reward circuits. However, imaging studies in addictive behaviours have identified a key involvement of the prefrontal cortex (PFC) both through its regulation of limbic reward regions and its involvement in higher-order executive function (for example, self-control, salience attribution and awareness). This Review focuses on functional neuroimaging studies conducted in the past decade that have expanded our understanding of the involvement of the PFC in drug addiction. Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of free will
   
     
   

Helene Benveniste & Nora Volkow
(If it was you, Helene, who lured Nora Volkow to Copenhagen, thanks!!)

   
Helene was  first author of a pioneering and very important paper on microdialysis assessment of glutamate (Benveniste, H., Drejer, J., Schousboe, A., & Diemer, N. H. (1984). Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. Journal of Neurochemistry, 43, 1369-1374). For the last 25 years, however, she has worked at the Brookhaven National Laboratory, Upton, New York, where also Nora Volkow worked until 2003. Joint papers include: Benveniste, H. & Volkow, N. D. (2013). Dopamine-enhancing medications to accelerate emergence from general anesthesia. Anesthesiology, 118, 5-6.; Benveniste, H., Fowler, J. S., Rooney, W. D., Scharf, B. A., Backus, W. W., Izrailtyan, I. et al. (2010). Cocaine is pharmacologically active in the nonhuman primate fetal brain. Proceedings of the National Academy of Sciences of the United States of America, 107, 1582-1587. Volkow, N. D., Fowler, J. S., Wang, G. J., Telang, F., Logan, J., Wong, C. et al. (2008). Methylphenidate decreased the amount of glucose needed by the brain to perform a cognitive task. PLoS.ONE., 3, e2017.  Benveniste, H., Fowler, J. S., Rooney, W., Ding, Y. S., Baumann, A. L., Moller, D. H. et al. (2005). Maternal and fetal 11C-cocaine uptake and kinetics measured in vivo by combined PET and MRI in pregnant nonhuman primates. Journal of Nuclear Medicine, 46, 312-320.    
 

 

Nora Volkow has great intensity and does seem to have an unusually concentrated mind. She is the author of more than 600 journal articles and book chapters, and in a great many of them first author. She is also first author of very many review articles in leading journals. In addition to addiction, there are important reviews of ADHD and obesity by Volkow.

 

 

 

 

 

 

 
     

Nora Volkow
&
Natasja Tolstoy

 

Both have russian roots. Nora is the grandchild of Leon Trotsky (and grew up in Mexico), and Natasja is a (very distant) relative of Leo Tolstoy. Natasja is a student in Molecular Biology affiliated to the Dept. of Neuroscience and Pharmacology

 
     
.. also at the lecture:    
 

Per Roland

Per Roland is now at the Dept. of Neuroscience and Pharmacology after a long career at Karolinska in Stockholm.

Per did important work in functional neuroimaging in pre-fMRI-times, and his book "Brain activation" published in 1993 by Wiley was much acclaimed.

I thought it appropriate to photograph him with a reflection of Rigshospitalet in the Faculty Club glass. This is where I first met him in 1972 at the 8th floor. There, in the departments of neurology and neurosurgery, Per did his pioneering studies on somatosensory detection and discrimination.

 
     

Paul Cumming

 

 

 

Paul splits his time between Erlangen and Copenhagen. His work is in neuroimaging, mainly of the dopamine system.

 

 

 

 

 

 
     
Photographs: Anders.Gade@psy.ku.dk