title: Exposure to opiates in female adolescents alters mu opiate receptor expression and increases the rewarding effects of morphine in future offspring.
abstract: Prescription opiate use and abuse has increased dramatically over the past two decades, including increased use in adolescent populations. Recently, it has been proposed that use during this critical period may affect future offspring even when use is discontinued prior to conception. Here, we utilize a rodent model to examine the effects of adolescent morphine exposure on the reward functioning of the offspring. Female Sprague Dawley rats were administered morphine for 10 days during early adolescence (post-natal day 30-39) using an escalating dosing regimen. Animals then remained drug free until adulthood at which point they were mated with naïve males. Adult offspring (F1 animals) were tested for their response to morphine-induced (0, 1, 2.5, 5, and 10 mg/kg, s.c.) conditioned place preference (CPP) and context-independent morphine-induced sensitization. Naïve littermates were used to examine mu opiate receptor expression in the nucleus accumbens and ventral tegmental area. Results indicate that F1 females whose mothers were exposed to morphine during adolescence (Mor-F1) demonstrate significantly enhanced CPP to the lowest doses of morphine compared with Sal-F1 females. There were no differences in context-independent sensitization between maternal treatment groups. Protein expression analysis showed significantly increased levels of accumbal mu opiate receptor in Mor-F1 offspring and decreased levels in the VTA. Taken together, these findings demonstrate a shift in the dose response curve with regard to the rewarding effects of morphine in Mor-F1 females which may in part be due to altered mu opiate receptor expression in the nucleus accumbens and VTA.
authors.affiliation: Department of Biomedical Sciences, Cummings School of Veterinary Medicine, Tufts University, Peabody Pavilion, 200 Westborough Road, Grafton, MA 01536, USA. Electronic address: fair.vassoler@tufts.edu.
authors.forename: Fair M
authors.initials: FM
authors.lastname: Vassoler
authors.affiliation: Department of Biomedical Sciences, Cummings School of Veterinary Medicine, Tufts University, Peabody Pavilion, 200 Westborough Road, Grafton, MA 01536, USA.
authors.forename: Siobhan J
authors.initials: SJ
authors.lastname: Wright
authors.affiliation: Department of Biomedical Sciences, Cummings School of Veterinary Medicine, Tufts University, Peabody Pavilion, 200 Westborough Road, Grafton, MA 01536, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Byrnes
mesh_terms: D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism*; D012201:Reward; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism*
chemical_list: D017450:Receptors, Opioid, mu; D009020:Morphine
keywords: Adolescence; Conditioned place preference; Morphine; Mu opioid receptor; NAc; Opiates; Opioids; Sensitization; Transgenerational; VTA