Adolescent morphine exposure increases nociceptive behaviors in rat model of formalin test

Abstract

The number of adolescents who use illicit drugs has increased dramatically. Adolescence is a critical period for brain development and maturation. The importance of the study of pain perception and the possible mechanisms involved is crystal clear. Up until now, there has been no evidence regarding the long‐term effect of adolescence morphine administration on pain perception. The objective of the present study was to investigate long‐lasting effect of adolescent morphine exposure on pain perception as well as analgesic response to a single dose of morphine injection. Adolescent and adult rats received morphine or saline, and then after 30 days of washout period, formalin test was performed. To evaluate morphine analgesia, in a separate group of animals, formalin test was performed after injection of a single dose of morphine during adulthood. The results demonstrated that the adolescent rats treated by morphine exhibited higher pain‐related behaviors compared to the control group, while the same results were not observed in adult rats that had been treated by morphine. Moreover, there was no significant difference in analgesic response to a single dose of morphine between two experimental groups. This study demonstrates enduring effect of morphine exposure during adolescence on pain perception.

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

“…The results of our laboratory study also showed that pain‐related behaviors were higher in morphine‐treated adolescents compared with morphine‐treated adult animals. These results confirm the sensitivity of adolescence to morphine exposure compared to adulthood (Ghasemi, Pachenari, Semnanian, & Azizi, 2019). On the other hand, some studies have acknowledged that substance use during adolescence does not have long‐lasting effects on the expression of anxiety‐like behaviors in adulthood (Bortolato et al., 2014; Higuera‐Matas et al., 2009; Rubino et al., 2008).…”

Adolescent morphine exposure changes the endogenous vlPAG opioid response to inflammatory pain in rats

“…We also found in another study that the morphine administration during adolescence, rather than in adulthood, has a lasting effect on nociceptive behaviors. The adolescent morphine-treated animals exhibited a higher nociceptive score in all three phases of the formalin test compared to the adolescent saline-treated group (Ghasemi et al, 2019).…”

“…Numerous studies have revealed the long-lasting effects of opioids, especially morphine exposure during adolescence, on various physiological functions, such as learning, memory, anxiety, and pain perception (Ghasemi et al, 2019;Khani et al, 2022aKhani et al, , 2022bKhani et al, , 2023Pachenari et al, 2018;Salmanzadeh et al, 2020Salmanzadeh et al, , 2021. A previous study from our laboratory demonstrated that adolescent morphine exposure (AME) influences pain behaviors in subsequent generations.…”

Adolescent opioid abuse: Role of glial and neuroimmune mechanisms

“…Results from behavioral tests, related to reaction-time, 24 h and 25 days after administration of morphine to adolescent rats found a profound effect on motor impulsive behavior later in adulthood (Moazen et al, 2018). Regarding pharmacological effects of chronic morphine administration during adolescence, this treatment increased pain responsiveness, in the formalin test, in adult rats compared to controls (Ghasemi et al, 2018). Adolescent oxycodone exposure resulted in increased sensitivity to the rewarding effects of opioids in adult mice (Sanchez et al, 2016).…”