Rationale: Parental drug use around or before conception can have adverse consequences for offspring. Historically, this research has focused on the effects of maternal substance use on future generations but less is known about the influence of the paternal lineage. This study focused on the impact of chronic paternal morphine exposure prior to conception on behavioral outcomes in male and female progeny. Objectives: This study sought to investigate the impact of paternal morphine self-administration on anxiety-like behavior, the stress response, and memory in male and female offspring. Methods: Adult, drug-naïve male and female progeny of morphine-treated sires and controls were evaluated for anxiety-like behavior using defensive probe burying and novelty-induced hypophagia paradigms. Hypothalamic-pituitary-adrenal (HPA) axis function was assessed by measuring plasma corticosterone levels following a restraint stressor in male and female progeny. Memory was probed using a battery of tests including object location memory, novel object recognition and contextual fear conditioning. Results: Paternal morphine exposure did not alter anxiety-like behavior or stress-induced HPA axis activation in male or female offspring. Morphine-sired male and female offspring showed intact hippocampus-dependent memory: they performed normally on the long-term fear conditioning and object location memory tests. In contrast, paternal morphine exposure selectively disrupted novel object recognition in female, but not male progeny. Conclusions: Our findings demonstrate that paternal morphine taking produces sex-specific and selective impairments in object recognition memory while leaving hippocampal function largely intact.

Paternal environmental perturbations can influence the physiology and behavior of offspring. For example, our previous work showed reduced cocaine reinforcement in male, but not female, progeny of rat sires that self-administered cocaine. The information transfer from sire to progeny may occur through epigenetic marks in sperm, encompassing alterations in small noncoding RNAs, including microRNAs (miRNAs) and/or DNA methylation. Here, no reliable changes in miRNAs in the sperm of cocaine-relative to saline-experienced sires were identified. In contrast, 272 differentially methylated regions were observed in sperm between these groups. Two hypomethylated promoter regions in the sperm of cocaine-experienced rats were upstream of cyclin-dependent kinase inhibitor 1a (Cdkn1a). Cdkn1a mRNA also was selectively increased in the NAc of cocaine-sired male (but not female) offspring. Cocaine selfadministration also enhanced Cdkn1a expression in the accumbens of cocaine-sired rats. These results suggest that changes in Cdkn1a may play a role in the reduced cocaine reinforcing efficacy observed in cocaine-sired male rats. Introducing a 90 d delay between sire self-administration and breeding reversed both cocaine resistance and the increase in accumbens Cdkn1a mRNA in male offspring, indicating that cocaine-induced epigenetic modifications are eliminated with sperm turnover. Collectively, our results indicate that cocaine self-administration produces hypomethylation of Cdkn1a in sperm and a selective increase in the expression of this gene in the NAc of male offspring, which is associated with blunted cocaine reinforcement.

Objectives/Hypothesis Hearing plays an important role in the maintenance of vocal control in normal individuals. In patients with spasmodic dysphonia (SD), however, the ability to maintain sustained control of phonation is impaired. The origins of SD are unknown, and it is unclear whether auditory feedback‐dependent vocal control is compromised in these patients. Study Design Prospective case‐control study. Methods We tested 15 SD patients and 11 age‐matched controls. Voice recordings were performed while subjects repeated the vowel /e/ and auditory feedback of their vocal sounds was altered in real‐time to introduce a pitch‐shift (±2 semitones), presented back to subjects using headphones. Recordings were analyzed to determine voice changes following the pitch‐shifted feedback. Results were further compared with patient demographics and subjective measures of dysphonia, including the Voice Handicap Index (VHI). Results Despite considerable pitch variability and vocal breaks, SD patients exhibited significantly higher average vocal pitch compensation than control subjects. SD patients also exhibited greater variability than controls. However, there were no significant correlations between vocal compensation and patient demographics, although there was a significant inverse correlation with VHI. Conclusions In this pilot study, patients with SD exhibited increased sensitivity to altered auditory feedback during sustained phonation. These results are consistent with recent theories of SD as a disorder of sensory‐motor feedback processing, and suggest possible avenues for future investigation. Level of Evidence 3 Laryngoscope, 131:2070–2075, 2021

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Highlights d Sleep deprivation improves memory in old mice but worsens it in young ones d Sleep deprivation decreases hippocampal flexibility and spindle counts in young mice d Increased spindle counts are associated with improved memory in old mice d Sleep deprivation improves the quality of hippocampal representations in old mice