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.

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Opioid and sucrose craving are accompanied by unique behavioral and affective profiles after extended abstinence in male and female rats

A powerful motivation to seek opioids remains after drug cessation and intensifies during extended periods of abstinence. Unfortunately, biomarkers associated with continued drug seeking have not been described. Moreover, previous studies have focused on the effects of early abstinence with little exploration into the long-term drug-induced mechanisms that occur after extended abstinence. Here we demonstrated that 30 days (D) of forced abstinence results in a time-dependent increase in morphine seeking in a rat model of morphine selfadministration (SA). We measured expression of known drug-responsive microRNAs (miRNAs) in the nucleus accumbens, an area critical for rewardrelated plasticity, during early or late abstinence in animals that underwent either a cue-induced relapse test or no relapse test. miRNAs are small noncoding RNAs that represent suitable biomarker candidates due to their longlasting nature. mir-32-5p levels during early abstinence negatively correlated with active lever pressing in both cue-exposed and cue-naïve animals. mir-1298-5p positively correlated with drug SA history after a relapse test during late abstinence. When animals underwent acute abstinence with no relapse test, mir-1298-5p correlated with drug infusions and active lever pressing during SA. In late abstinence with no relapse test, mir-137-3p negatively correlated with drug infusions. Regulation of mir-32-5p target genes and significant correlation of target gene mRNA with mir-32-5p was observed after abstinence. These results indicate that lasting regulation of miRNA expression is associated with drug intake following morphine SA. In addition, we conclude

Future research needs to be directed at the long-term maintenance treatment and to address questions about which drugs should be used, in what combinations, and with what frequencies.

Background: A growing body of preclinical studies report that preconceptional experiences can have a profound and long-lasting impact on adult offspring behavior and physiology. However, less is known about paternal drug exposure and its effects on reward sensitivity in the next generation. Methods: Adult male rats self-administered morphine for 65 days; controls received saline. Sires were bred to drug-naive dams to produce first-generation (F1) offspring. Morphine, cocaine, and nicotine self-administration were measured in adult F1 progeny. Molecular correlates of addiction-like behaviors were measured in reward-related brain regions of drug naive F1 offspring. Results: Male, but not female offspring produced by morphine-exposed sires exhibited dose-dependent increased morphine self-administration and increased motivation to earn morphine infusions under a progressive ratio schedule of reinforcement. This phenotype was drug-specific as self-administration of cocaine, nicotine, and sucrose were not altered by paternal morphine history. The male offspring of morphine-exposed sires also had increased expression of mu-opioid receptors in the ventral tegmental area but not in the nucleus accumbens. Conclusions: Paternal morphine exposure increased morphine addiction-like behavioral vulnerability in male but not female progeny. This phenotype is likely driven by long-lasting neural adaptations within the reward neural brain pathways.

In summary, patient choice should include the form of sedation or topical anaesthesia in endoscopic practice. The development of a decision tree is an effective way of providing information and recording a patient's choice.

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