Parental morphine exposure affects repetitive grooming actions and marble burying behavior in the offspring: Potential relevance for obsessive-compulsive like behavior

Eur J Pharmacol. 2019 Dec 15:865:172757. doi: 10.1016/j.ejphar.2019.172757. Epub 2019 Nov 3.

Abstract

Family, adoption and twin studies have highlighted the significant role of heritable influences on individual differences in opioid addiction. Meanwhile, obsessive-compulsive disorder (OCD) is a disorder wherein the individual experiences recurring thoughts that cause irrational fears and anxiety. In the present study, adult male and female rats received morphine solution for 21 days and were drug-free for 10 days. Offspring were used in 4 distinct groups; (1) paternal morphine-exposed, (2) maternal morphine-exposed, (3) maternal and paternal morphine-exposed, and (4) drug-naïve subjects. We assessed the grooming behavior and marble burying test as an indicator of obsessive-compulsive behavior. To clarify the mechanisms underlying these changes, the mRNA level of BDNF, the phosphorylation level of CREB and the protein level of D2 dopamine receptor (DR) were evaluated in the nucleus accumbens (NAc). The grooming behavior in male offspring with one or two morphine-abstinent parent(s) increased compared with the offspring of drug naïve rats. In addition, the offspring of morphine-exposed parents buried more marbles when compared with the offspring of drug-naïve parents. Also, the BDNF mRNA was down-regulated in the NAC. However, the levels of phospho-CREB and D2 DR were elevated. Previous studies indicated that exposure to morphine in adulthood enhances the risk of psychiatric disorders in offspring. OCD is one the comorbid disorders with addiction and increases the risk of substance abuse disorder in patients. In this survey, we found that morphine exposure in parents before gestation can encourage obsessive-compulsive behavior in offspring.

Keywords: Addiction; Grooming behavior; Obsessive-compulsive disorder; Offspring; Opioid.

MeSH terms

  • Analgesics, Opioid / adverse effects*
  • Animals
  • Behavior, Animal / drug effects*
  • Brain-Derived Neurotrophic Factor / genetics
  • Compulsive Behavior / chemically induced*
  • Compulsive Behavior / metabolism
  • Disease Models, Animal
  • Female
  • Grooming / drug effects
  • Male
  • Maternal-Fetal Exchange
  • Morphine / adverse effects*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Obsessive-Compulsive Disorder / chemically induced*
  • Obsessive-Compulsive Disorder / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats, Wistar
  • Receptors, Dopamine D2 / metabolism

Substances

  • Analgesics, Opioid
  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • Receptors, Dopamine D2
  • Morphine