Paternal morphine self-administration produces object recognition memory deficits in female, but not male offspring

Abstract

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.

A Sensitive Homecage-Based Novel Object Recognition Task for Rodents

“…A major advantage of the task is that it can be used in both rats and mice (Agarwal et al, 2020;Chang et al, 2020). Current iterations of the NOR paradigm are widely used to study memory (Cole et al, 2020), synaptic plasticity (Lee et al, 2020), impairment and/or recovery of function in brain disease (Grayson et al, 2015), TBI (Amoros-Aguilar et al, 2020), stress (Brivio et al, 2020;Glushchak et al, 2021), aging (Amirazodi et al, 2020), sleep (Shahveisi et al, 2020), autism (Batista et al, 2019;Gandhi and Lee, 2020), and epigenetics (Ellis et al, 2020;Sadat-Shirazi et al, 2020).…”

Maternal Oxycodone Treatment Results in Neurobehavioral Disruptions in Mice Offspring

“…Rat offspring derived from female and male parents treated with morphine exhibit memory deficiency that is presumably because of suppression of long-term potentiation in the hippocampus ( Sarkaki et al, 2008 ). Paternal exposure of Sprague Dawley rats to morphine impairs novel-object recognition in female but not male progeny ( Ellis et al, 2020 ).…”

Generational Effects of Opioid Exposure

“…These changes were not seen in the female F1 and F2 progeny, suggesting sex-specific alterations resulting from maternal adult morphine exposure. Ellis et al have also shown that paternal morphine exposure produces sex-specific impairments in object recognition memory in female offspring [72]. Additionally, offspring born to parents with adult morphine exposure had decreased object recognition, possibly due to decreased histone H3 acetylation and ∆FosB levels in the PFC and hippocampus [73].…”