Morphine exposure and maternal deprivation during the early postnatal period alter neuromotor development and nerve growth factor levels

Abstract

The objective of this study was to verify whether repeated morphine administration and maternal deprivation in early life alter neurobehavioral development and central nerve growth factor (NGF) levels. A total of 58 male Wistar rat pups were used in our study. From postnatal day 1 (P1), litters were daily deprived of their mother for 3h; this was continued for the first 10days of life. Animals were divided into 5 groups: total control (C), did not receive any intervention; saline (S), received saline solution; morphine (M), received morphine; deprived-saline group (DS), were subjected to maternal deprivation and received saline solution; and deprived-morphine (DM), were subjected to maternal deprivation and received morphine. From P8, newborns received subcutaneous (s.c.) injections of morphine or saline (5μg) once daily for 7days. Righting reflex, negative geotaxis and gait were chosen as postural parameters to evaluate neuromotor reflexes. In the righting reflex test, a delay in the development of animals was evidenced in the M group. Performance of negative geotaxis was slower in the M and DM groups. In the gait test, all groups showed a daily improvement in performance in terms of locomotion frequency. An increased frequency of rearing was observed in the M, DS, and DM groups from P16 to P20. The DM group presented an increase in NGF levels in the brainstem. An increase in cerebral cortex NGF levels in the M, DS, and DM groups was observed as well. Our results suggest that changes in environmental conditions and the disruption of mother-infant interactions during the neonatal period can produce changes in the neurobiology, physiology, and emotional behavior of rats. This finding has important implications for the maternal-neonate interaction needed for normal brain development in newborns.

Maternal deprivation alters nociceptive response in a gender‐dependent manner in rats

“…Briefly, pups were placed in a supine position and their latency time to turn over their longitudinal axis to restore a normal prone position was measured. Such a task was considered to be fully achieved when the pups turned of 180° around their longitudinal axis and when their four paws were in contact with the plane surface within the observed 120‐s timeframe (Karalis et al, 2011; de Oliveira et al, 2017).…”

“…The latency time tobothturn aroundof 180° to face upwards and climb up the board with their forepaws reaching the upper edge of the board was measured. Finally, thetest results were considered to be negative when the pups did not succeed in such a task within 120 s (Horvath et al, 2013; de Oliveira et al, 2017).…”

“…Environmental alterations during the neonatal period seem to play a fundamental role in the establishment of the neurobiological factors controlling both behavior and stress responsiveness (Marco et al, 2009). With regards to postnatal stressor events, postnatal maternal deprivation is known to be one of the most powerful stressors during development, as it can trigger long‐lasting neurobiological effects (Fuentes et al, 2014; Gracia‐Rubio et al, 2016; de Oliveira et al, 2017). Although previous studies documented the appearance of maternal deprivation‐related effects to be highly age‐dependent (Lehmann et al, 2002; Loi et al, 2014), few data regarding the possible gender‐dependent effects of an adverse neonatal episode (e.g., maternal deprivation) exist.…”

“…Environmental alterations during the neonatal period seem to play a fundamental role in the establishment of the neurobiological factors controlling both behavior and stress responsiveness (Marco et al, 2009). With regards to postnatal stressor events, postnatal maternal deprivation is known to be one of the most powerful stressors during development, as it can trigger long-lasting neurobiological effects (Fuentes et al, 2014;Gracia-Rubio et al, 2016;de Oliveira et al, to investigate the effects of stress on the offspring's behavior and physiology (Aguggia et al, 2013). Commonly, the offspring exposed to alterations in mother-pup interaction reports long-lasting modifications of both behavior and developmental parameters (Pryce and Feldon, 2003).…”

Brain‐derived neurotrophic factor and nerve growth factor concentrations in maternal and umbilical cord blood of opium‐addicted mothers

“…Several studies have revealed that opioid exposure during pregnancy in rodents leads to changes in BDNF and NGF levels in the brain of offspring, and thus, neurobehavioral defects (Ahmadalipour, Ghodrati‐Jaldbakhan, Samaei, & Rashidy‐Pour, 2018; Oliveira et al, 2017; Wu et al, 2014; Wu, Mo, Yabe, Schwartz, & Robinson, 2001).…”