Image-guided cranial irradiation-induced ablation of dentate gyrus neurogenesis impairs extinction of recent morphine reward memories.

Dentate gyrus adult neurogenesis is implicated in the formation of hippocampal-dependent contextual associations. However, the role of adult neurogenesis during reward-based context-dependent paradigms-such as conditioned place preference (CPP)-is understudied. Therefore, we used image-guided, hippocampal-targeted X-ray irradiation (IG-IR) and morphine CPP to explore whether dentate gyrus adult neurogenesis plays a role in reward memories created in adult C57BL/6J male mice. In addition, as adult neurogenesis appears to participate to a greater extent in retrieval and extinction of recent (<48 hr posttraining) versus remote (>1 week posttraining) memories, we specifically examined the role of adult neurogenesis in reward-associated contextual memories probed at recent and remote timepoints. Six weeks post-IG-IR or Sham treatment, mice underwent morphine CPP. Using separate groups, retrieval of recent and remote reward memories was found to be similar between IG-IR and Sham treatments. Interestingly, IG-IR mice showed impaired extinction-or increased persistence-of the morphine-associated reward memory when it was probed 24-hr (recent) but not 3-weeks (remote) postconditioning relative to Sham mice. Taken together, these data show that hippocampal-directed irradiation and the associated decrease in dentate gyrus adult neurogenesis affect the persistence of recently-but not remotely-probed reward memory. These data indicate a novel role for adult neurogenesis in reward-based memories and particularly the extinction rate of these memories. Consideration of this work may lead to better understanding of extinction-based behavioral interventions for psychiatric conditions characterized by dysregulated reward processing.

Effects of familial risk and stimulant drug use on the anticipation of monetary reward: an fMRI study.

The association between stimulant drug use and aberrant reward processing is well-documented in the literature, but the nature of these abnormalities remains elusive. The present study aims to disentangle the separate and interacting effects of stimulant drug use and pre-existing familial risk on abnormal reward processing associated with stimulant drug addiction. We used the Monetary Incentive Delay task, a well-validated measure of reward processing, during fMRI scanning in four distinct groups: individuals with familial risk who were either stimulant drug-dependent (N = 41) or had never used stimulant drugs (N = 46); and individuals without familial risk who were either using stimulant drugs (N = 25) or not (N = 48). We first examined task-related whole-brain activation followed by a psychophysiological interaction analysis to further explore brain functional connectivity. For analyses, we used a univariate model with two fixed factors (familial risk and stimulant drug use). Our results showed increased task-related activation in the putamen and motor cortex of stimulant-using participants. We also found altered task-related functional connectivity between the putamen and frontal regions in participants with a familial risk (irrespective of whether they were using stimulant drugs or not). Additionally, we identified an interaction between stimulant drug use and familial risk in task-related functional connectivity between the putamen and motor-related cortical regions in potentially at-risk individuals. Our findings suggest that abnormal task-related activation in motor brain systems is associated with regular stimulant drug use, whereas abnormal task-related functional connectivity in frontostriatal brain systems, in individuals with familial risk, may indicate pre-existing neural vulnerability for developing addiction.