Preconception paternal morphine exposure leads to an impulsive phenotype in male rat progenyVise andre og tillknytning
2021 (engelsk)Inngår i: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 238, s. 3435-3446Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]
Rationale Identifying the long-term neurocognitive implications of opioid addiction may further our understanding of the compulsive nature of this brain disorder. The aim of this study was to examine the effects of paternal adolescent opiate exposure on cognitive performance (visual attention, impulsivity, and compulsivity) in the next generation. Methods Male Wistar rats received escalating doses of morphine (2.5-25 mg/kg, s.c.) or saline for 10 days during adolescence (P30-39). In adulthood (P70-80), these rats were allowed to mate with drug-naive females. Male offspring from morphine- and saline-exposed sires, once in adulthood, were trained and tested in the 5-choice serial reaction time test (5-CSRTT) to evaluate their cognitive abilities under baseline, drug-free conditions as well as following acute (1, 3, 5 mg/kg morphine) and subchronic morphine (5 mg/kg morphine for 5 days) treatment. Behavioral effects of the opioid receptor antagonist naloxone were also assessed. Results Morphine-sired offspring exhibited delayed learning when the shortest stimulus duration (1 s) was introduced, i.e., when cognitive load was highest. These subjects also exhibited a reduced ability to exert inhibitory control, as reflected by increased premature and perseverative responding under drug-free baseline conditions in comparison to saline-sired rats. These impairments could not be reversed by administration of naloxone. Moreover, impulsive behavior was further enhanced in morphine-sired rats following acute and subchronic morphine treatment. Conclusion Paternal opiate exposure during adolescence was found to primarily impair inhibitory control in male progeny. These results further our understanding of the long-term costs and risk of opioid abuse, extending across generations.
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Springer Nature, 2021. Vol. 238, s. 3435-3446
Emneord [en]
Transgenerational; Paternal drug exposure; Adolescence; Opioid; Executive function; Impulsive action; Waiting impulsivity
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Identifikatorer
URN: urn:nbn:se:liu:diva-178939DOI: 10.1007/s00213-021-05962-0ISI: 000687907400003PubMedID: 34427719OAI: oai:DiVA.org:liu-178939DiVA, id: diva2:1591318
Merknad
Funding Agencies|Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
2021-09-062021-09-062022-04-07