Long-term behavioral effects in a rat model of prolonged postnatal morphine exposure.

Abstract

Prolonged morphine treatment in neonatal pediatric populations is associated with a high incidence of opioid tolerance and dependence. Despite the clinical relevance of this problem, our knowledge of the long-term consequences is sparse. The main objective of this study was to investigate whether prolonged morphine administration in a neonatal rat is associated with long-term behavioral changes in adulthood. Newborn animals received either morphine (10mg/kg) or equal volume of saline subcutaneously twice daily for the first 2 weeks of life. Morphine treated animals underwent 10 days of morphine weaning to reduce the potential for observable physical signs of withdrawal. Animals were subjected to non-stressful testing (locomotor activity recording and a Novel-Object Recognition test) at a young age (PD27-31) or later in adulthood (PD55-56), as well as stressful testing (calibrated forceps test, Hot Plate test, and Forced Swim test) only in adulthood. Analysis revealed that prolonged neonatal morphine exposure resulted in decreased thermal, but not mechanical threshold. Importantly, no differences were found for total locomotor activity (proxy of drug reward/reinforcement behavior), individual Forced Swim test behaviors (proxy of affective processing), or Novel-Object Recognition test. Performance on the Novel-Object Recognition test was compromised in the morphine treated group at the young age, however the effect disappeared in adulthood. These novel results provide insight into the long-term consequences of opioid treatment during an early developmental period and suggest long-term neuroplastic differences in sensory processing related to thermal stimuli.

Morphine exposure during early life alters thermal and mechanical thresholds in rats

“…Similar to our study, Craig and Bajic (2015) conducted an experiment in which rats were subjected to morphine (10 mg/kg) twice daily for the first two weeks of life. They observed a decrease in the thermal threshold, but not the mechanical threshold, at adult age.…”

Adult rat morphine exposure changes morphine preference, anxiety, and the brain expression of dopamine receptors in male offspring

“…Ten male and ten female adult Wistar rats received subcutaneous injections of morphine sulfate (10 mg/kg) twice daily (at 7 a.m. and 7 p.m.) for 14 days (Craig and Bajic, 2015). Control animals (10 males and 10 females) received saline injections at the times and intervals similar to the morphine group.…”

Efficacy of Intrathecal Morphine in a Model of Surgical Pain in Rats

“…This finding is contrary to the common belief that opioids alter the behaviour of pain-free rodents [38]. Morphine as well as other opioids do influence the behaviours of pain-free rats, but this has generally been reported when the doses used are much greater than those recommended for clinical use in rats [14,38], or when opioids are administered repeatedly for example in models of opioid tolerance [53,54]. The activity of all rats decreased over time, regardless of the drug received (NaCl or morphine).…”