Does Morphine Exposure Before Gestation Change AnxietyLike Behavior During Morphine Dependence in Male Wistar Rats?


1 Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran

2 Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Amir-Almomenin Hospital, Islamic Azad University, Tehran, Iran

3 1. Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran 2. Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Amir-Almomenin Hospital, Islamic Azad University, Tehran, Iran 3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran



Background: Anxiety is one of the comorbid disorders of opioid addiction, which leads to opioid abuse or persuades people to 
engage in opioid abuse. Evidence revealed that morphine exposure before conception changes the offspring’s phenotype. The 
current study aimed to investigate the influence of morphine dependence and abstinence on anxiety-like behavior in morphineexposed and drug-naïve offspring.
Methods: Adult male and female rats were treated with morphine or vehicle for 21 days. Then, all rats were left without drug 
treatment for 10 days. A morphine-exposed female rat was mated with either a vehicle-exposed or morphine-abstinent male. 
According to parental morphine exposure, the offspring were categorized into four distinct groups: (1) control (both drug-naïve 
parents), (2) paternal morphine-exposed, (3) maternal morphine-exposed, and (4) biparental morphine-exposed. The anxiety-like 
behavior was measured in adult male offspring using open field and elevated plus-maze tests before morphine exposure (naïve), 21 
days after morphine exposure (dependence), and ten days after the last morphine exposure (abstinence). 
Findings: The results indicated that anxiety-like behavior increased before morphine exposure in maternal and biparental morphineexposed offspring (P<0.05). However, after morphine exposure, the anxiety level did not change among the groups. Ten days after 
the last morphine exposure, anxiety-like behavior increased only in biparental morphine-exposed offspring (P<0.05). 
Conclusion: The offspring of morphine-abstinent parents exhibited an anxious phenotype. Disruption of the HPA axis was seen in 
the progeny of maternal and biparental morphine-exposed rats. Indeed, morphine exposure for 21 days did not change anxiety-like 
behavior in these offspring which might be correlated to disruption of HPA axis in them. 


Saba Sabzevari: (Google Scholar) (PubMed)

Kiyana Rohbani: (Google Scholar) (PubMed)

Mahsa Sadeghi-Adl: (Google Scholar) (PubMed)

Solmaz Khalifeh: (Google Scholar) (PubMed)

Mitra-Sadat Sadat-Shirazi: (Google Scholar) (PubMed)

Mohammad-Reza Zarrindast: (Google Scholar) (PubMed)




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