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Comparison and Interaction of Morphine and Cb1 Agonist Conditioned Place Preference in the Rat Model of Early Life Stress Publisher Pubmed



Pirri F1, 2 ; Akbarabadi A2 ; Sadatshirazi MS2 ; Nouri Zadehtehrani S2 ; Mahboubi S2 ; Karimi Goudarzi A1 ; Zarrindast MR2, 3, 4
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Authors Affiliations
  1. 1. Department of Basic Sciences, College of Veterinary Medicine, Islamic Azad University, Alborz, Iran
  2. 2. Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Endocrinology and Metabolism Research Institute, Tehran University of Medical Science, Tehran, Iran

Source: International Journal of Developmental Neuroscience Published:2021


Abstract

Early life stress (ELS) disrupts brain development and subsequently affects physical and psychological health. ELS has been associated with an increased risk of relapse and inadequate treatment response in addicted patients. The current study was designed to find the effect of ELS on the rewarding effect of morphine and cannabinoid and their interaction. Pregnant female Wistar rats were used in this study. On postnatal day 2 (PND2), pups were separated from their mothers for 3 hr daily. This procedure was repeated every day at the same time until PND 14. The control group was kept in the standard nesting way with their mothers. The adult male offspring of maternal separated (MS) and standard nested (SN) rats were used. Using conditioned place preference task (CPP), the rewarding effect of morphine (0.75, 1.25, 2.5, and 5 mg/kg) was evaluated in both MS and SN groups. Besides, the rewarding effect of cannabinoids was investigated using the administration of CB1 receptor agonist (ACPA, 0.25, 0.5, 1 µg/rat) and inverse agonist (AM-251, 30, 60, and 90 ng/rat) in the nucleus accumbens (NAc). To evaluate the interaction between NAc cannabinoidergic system and morphine, the noneffective dose of ACPA and AM-251 were administered with a noneffective dose of morphine (0.75 mg/kg) on both MS and SN animals. Obtained results indicated that MS groups had a leftward shift in the rewarding effect of morphine and conditioned with low doses of morphine. However, they had a rightward shift in the rewarding effect of cannabinoids. In addition, coadministration of noneffective doses of morphine and ACPA potentiate conditioning in both MS and SN groups. Previous evidence shows that ELS induced changes in the brain, especially in the reward circuits. Here, we demonstrated that MS animals are more sensitive to the rewarding effect of morphine compared with SN animals. In addition, ELS disrupts the cannabinoid system and affect the rewarding effect of cannabinoids. © 2021 International Society for Developmental Neuroscience
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