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Dietz, D. M.

Publications and source records attributed to Dietz, D. M..

2 recordsLinked to original sources

Environmental enrichment promotes adaptive responding during tests of behavioral regulation in male heterogeneous stock rats

Organisms must regulate their behavior flexibly in the face of environmental challenges. Failure can lead to a host of maladaptive behavioral traits associated with a range of neuropsychiatric disorders, including attention deficit hyperactivity disorder, autism, and substance use disorders. This maladaptive dysregulation of behavior is influenced by genetic and environmental factors. For example, environmental enrichment produces beneficial neurobehavioral effects in animal models of such disorders. The present study determined the effects of environmental enrichment on a range of measures related to behavioral regulation using a large cohort of male, outbred heterogeneous stock (HS) rats as subjects to mimic the genetic variability found in the human population. Subjects were reared from late adolescence onwards either in pairs in standard housing with minimal enrichment (n=200) or in groups of 16 in a highly enriched environment consisting of a large multi-level cage filled with toys, running wheels, and shelters (n=64). Rats were subjected to a battery of tests, including: (i) locomotor response to novelty, (iI) light reinforcement, (iii) social reinforcement, (iv) reaction time, (v) a patch-depletion foraging test, (vi) Pavlovian conditioned approach, (vii) conditioned reinforcement, and (viii) cocaine conditioned cue preference. Results indicated that rats housed in the enriched environment were able to filter out irrelevant stimuli more effectively and thereby regulate their behavior more efficiently than standard-housing rats. The dramatic impact of environmental enrichment suggests that behavioral studies using standard housing conditions may not generalize to more complex environments that may be more ethologically relevant.

animal behavior and cognition↗

Histone H3 dopaminylation in ventral tegmental area underlies heroin-induced maladaptive plasticity

Persistent transcriptional eventsamples were incubated on ice for 30 min and then centrifugeds in ventral tegmental area (VTA) and other reward relevant brain regions contribute to enduring behavioral adaptations that characterize substance use disorder (SUD). Recent data from our laboratory indicate that aberrant accumulation of the newly discovered histone post-translational modification (PTM), H3 dopaminylation at glutamine 5 (H3Q5dop), contributes significantly to cocaine-seeking behavior following prolonged periods of abstinence. It remained unclear, however, whether this modification is important for relapse vulnerability in the context of other drugs of abuse, such as opioids. Here, we showed that H3Q5dop plays a critical role in heroin-mediated transcriptional plasticity in midbrain. In rats undergoing abstinence from heroin self-administration (SA), we found acute and persistent accumulation of H3Q5dop in VTA. By attenuating H3Q5dop during abstinence, we both altered gene expression programs associated with heroin withdrawal and reduced heroin-primed reinstatement behavior. These findings thus establish an essential role for H3Q5dop, and its downstream transcriptional consequences, in opioid-induced plasticity in VTA. SIGNIFICANCE STATEMENTOpioid addiction is a chronically relapsing disorder defined by pathological drug-seeking behavior. Persistent relapse vulnerability is hypothesized to reflect a functional "rewiring" of reward-processing circuitry in the brain. This phenomenon is precipitated by drug-induced alterations in transcriptional plasticity of midbrain dopamine neurons, indicating an important role for epigenetic regulatory mechanisms in opioid dependence. We found that the newly discovered histone modification, H3 dopaminylation at glutamine 5 (H3Q5dop), was increased in ventral tegmental area (VTA) during periods of abstinence. H3Q5dop accumulation was found to regulate transcriptional programs associated with chronic heroin exposure. Using viral-mediated gene therapy to reduce H3Q5dop accumulation during abstinence resulted in attenuated heroin-primed seeking behaviors. Together, our results indicate that H3Q5dop plays an abstinence-specific role in regulating heroin-induced behavioral plasticity during prolonged abstinence.

neuroscience↗