A Genetic Polymorphism of the Endogenous Opioid Dynorphin Modulates Monetary Reward Anticipation in the Corticostriatal Loop

Abstract

The dynorphin/κ-opioid receptor (KOP-R) system has been shown to play a role in different types of behavior regulation, including reward-related behavior and drug craving. It has been shown that alleles with 3 or 4 repeats (HH genotype) of the variable nucleotide tandem repeat (68-bp VNTR) functional polymorphism of the prodynorphin (PDYN) gene are associated with higher levels of dynorphin peptides than alleles with 1 or 2 repeats (LL genotype). We used fMRI on N = 71 prescreened healthy participants to investigate the effect of this polymorphism on cerebral activation in the limbic-corticostriatal loop during reward anticipation. Individuals with the HH genotype showed higher activation than those with the LL genotype in the medial orbitofrontal cortex (mOFC) when anticipating a possible monetary reward. In addition, the HH genotype showed stronger functional coupling (as assessed by effective connectivity analyses) of mOFC with VMPFC, subgenual anterior cingulate cortex, and ventral striatum during reward anticipation. This hints at a larger sensitivity for upcoming rewards in individuals with the HH genotype, resulting in a higher motivation to attain these rewards. These findings provide first evidence in humans that the PDYN polymorphism modulates neural processes associated with the anticipation of rewards, which ultimately may help to explain differences between genotypes with respect to addiction and drug abuse.

Better you lose than I do: neural networks involved in winning and losing in a real time strictly competitive game

“…In addition, it activated the inferior frontal gyrus (IFG), inferior parietal lobe (IPL), and precuneus. The behavioral data demonstrated that participants were faster in reaction time to monetary cues comparing to non-monetary ones, which is in line with other studies which used similar task 20 21 . Before we interpret these findings in more detail, we will discuss the main effects and interaction results of our design.…”

A functional polymorphism in the prodynorphin gene affects cognitive flexibility and brain activation during reversal learning

“…However, when they applied damage to the fibers passing near or through the OFC, it caused an impairment of behavioral flexibility (Rudebeck et al, 2013 ). This is in line with our previous PDYN study (Votinov et al, 2014 ) which had also demonstrated a difference between genotype groups in functional connectivity between OFC and other regions.…”

“…Furthermore, similar to the effect on the striatum, KOR agonists also affect prefrontal cortex by decreasing dopamine overflow (Margolis et al, 2006 ; Tejeda et al, 2012 ). Our previous dynorphins study (Votinov et al, 2014 ) also demonstrated differences in the brain activation for medial orbitofrontal cortex between HH and LL genotype groups. In that study we observed that HH group had higher activation in mOFC than the LL group in response to upcoming monetary reward, which interpreted as increased reward sensitivity in the HH group.…”

“…To create ROIs for different subdivisions of the striatum (caudate, putamen, and ventral striatum), we used the anatomical templates for left, right putamen and left, right caudate from the WFU-PickAtlas (Version 3.3, Wake Forest University, School of Medicine, Winston-Salem, North Carolina; www.ansir.wfubmc.edu ). The masks for the left and right ventral striatum were defined in the same way as our previous dynorphins study (Votinov et al, 2014 ) by a conjunction of the “caudate head” template provided in the WFU-PickAtlas and the “accumbens” template taken from the Harvard–Oxford Subcortical Structural Atlas which is implemented in FSL software.…”

Blunted Endogenous Opioid Release Following an Oral Amphetamine Challenge in Pathological Gamblers

“…The underlying mechanism for clinical efficacy of opioid antagonists in alcoholism is generally described as blocking the increased MOR and β -endorphin stimulation of MOR in mesolimbic dopaminergic pathway thus reducing activity and the rewarding effects of alcohol and craving ( Johnson and North, 1992 ). Given our observation that MOR availability is unchanged in PG, the mechanism of action for opioid antagonists may therefore involve other opioid receptors such as kappa ( Votinov et al , 2014 ) or processes other than those involved in pleasure and reward, such as impulsivity.…”