Development of anxiety‐like behaviors during adolescence: Persistent effects of adolescent morphine exposure in male rats

Abstract

Epidemiological studies show the prevalence of opioid use, misuse and abuse in adolescents, which imposes social and economic accountability worldwide. Chronic opioid exposure, especially in adolescents, may have lasting effects on emotional behaviors that persist into adulthood. The current experiments were therefore designed to study the effects of sustained opioid exposure during adolescence on anxiety-like behaviors. Adolescent male Wistar rats underwent increasing doses of morphine for 10 days (PNDs 31-40). After that the open field test (OFT) and elevated plus maze (EPM) test were performed over a 4-week postmorphine treatment from adolescence to adulthood. Moreover, the weight of the animals was measured at these time points. We found that chronic adolescent morphine exposure reduces the weight gain during the period of morphine treatment and 4 weeks after that. It had no significant effect on the locomotor activity in the animals. Moreover, anxiolytic-like behavior was observed in the rats exposed to morphine during adolescence evaluated by OFT and EPM test.Thus, long-term exposure to morphine during adolescence has the profound potential of altering the anxiety-like behavior profile in the period from adolescence to adulthood. The maturation of the nervous system can be affected by drug abuse during the developmental window of adolescence and these effects may lead to behaviorally stable alterations.

Chronic morphine exposure and maternal separation induce impairments in cognition and locomotor activity of male adolescent rats

“…Increased anxiety‐like behavior and exploratory behaviors in MS mice had been reported before (Wang et al, 2015). It also has been shown that MS reduces the anxiety‐like behavior of adolescent rats in the OF test (Wang et al, 2015) or induces chronic changes in anxiety‐related behaviors (Kalinichev et al, 2000; Khani et al, 2022). On the other hand, MS can induce less anxiety‐like behavior in teenage rats (Wang et al, 2015).…”

“…It also increases reward‐induced behaviors (Abu & Roy, 2021; Fleites et al, 2022), escalations in dependence, withdrawal, and deliberately drinking morphine throughout gestation, body weight, anxiety‐like behavior, and global behavioral scores in mice (Fleites et al, 2022). Drug abuse throughout the developmental period of adolescence affects the maturation of the nervous system and therefore and may cause long‐term behavioral changes (Khani et al, 2022; Vassoler & Byrnes, 2021).…”

Acute adolescent morphine exposure improves dark avoidance memory and enhances long‐term potentiation of ventral hippocampal CA1 during adulthood in rats

“…33 Furthermore, our previous study presented the ineffectiveness of chronic adolescent morphine exposure on animal locomotor activity despite the reduction of anxiety-like behaviour from adolescence to adulthood. 8 According to human epidemiological studies, opioid addiction during adolescence is strongly associated with an increased risk of anxiety disorders throughout life. 34 However, contradictory results have been reported from the findings of others in the form of increased or decreased 35 emotional behavioural profiles, including anxiety-like behaviour during opioid exposure.…”

“…Therefore, this makes adolescents more vulnerable to the neurological consequences of opioid consumption compared with adults 7 . Opioid exposure during adolescence leads to disruption in the process of neural development and its specialization, resulting in permanent changes in the brain structure and cognitive function 8 …”

“…7 Opioid exposure during adolescence leads to disruption in the process of neural development and its specialization, resulting in permanent changes in the brain structure and cognitive function. 8 Hippocampus, a well-known brain site for learning and memory, is located in the medial temporal lobe. It undergoes significant developmental alterations during adolescence.…”