Opium Effect in Pregnancy on the Dynamics of Maternal Behavior: Testing a Neurochemical Model

Abstract

Background: Investigations into neurochemical mechanisms of opioid addiction are difficult due to the complexity of behavior and multiplicity of involved neurotransmitter and hormonal systems. The aim of this study was to examine the benefits of structured analysis of these mechanisms using the framework of the neurochemical model Functional Ensemble of Temperament (FET) and the example of maternal behavior under the condition of opium consumption in pregnancy. The FET differentiates between (a) endurance, (b) speed of integration, and (c) emotionality aspects of behavior suggesting that these systems are differentially regulated by (a) serotonin-neuropeptides-brain-derived neurotrophic factor (BDNF), (b) dopamine-GABA, and (c) opioid receptor systems, correspondingly. The FET also suggests that mu-opioid receptors (MORs) binding the endorphines (including opium’s ingredient morphine) have a stronger association with regulation endurance, whereas delta-OR have a stronger association with integration of behavior and kappa-OR – with the perceptual mobilization seen in anxiety. To test the predictions of this model, we compared the impact of massive MOR dysregulation on 3 behavioral aspects of behavior and on serotonin, BDNF, and corticosterone levels. Methods: The study used 24 female white Wistar rats which were randomly divided into (1) control group: pregnant rats without any intervention; (2) opium-exposed group: animals that were exposed to opium during pregnancy and after the delivery until the end of the study. At the end of the study, the levels of BDNF, serotonin (5-HT) in the hippocampus of the mother’s brain, and serum corticosterone, as well as 12 aspects of the maternal behavior were evaluated. The differences between control and experimental groups were assessed using the t test for independent samples. Results: The BDNF and serotonin concentrations in the hippocampus of the mother rats which were exposed to opium were lower than in the control group; the mean corticosterone in exposed mothers was higher than in the control group. Behaviorally, opium-consuming mothers showed lower endurance in 4 distinct behavioral categories (nesting, feeding, grooming, and retrieval) than the mothers in the control group. Ease of integration of behavior was affected to a lesser degree, showing a significant effect only in 1 out of 5 applied measures. Self-grooming, seen as an emotionality-related aspect of behavior, was not affected. Conclusion: Opium exposure during pregnancy in our experiment primarily reduced the endurance of rat’s maternal behavior, but the speed of integration of behavioral acts was less affected. This negative impact of opium on endurance was associated with a decrease of BDNF and serotonin levels in the hippocampus and an increase in corticosterone level in opium-consuming mothers. There is no effect of opium exposure on self-grooming behavior. This pattern supports the FET hypothesis about the role of 5-HT and BDNF in endurance, differential regulation of endurance, integrative and emotionality aspects of behavior, and differential association of the MOR system with endurance aspects, in comparison with kappa- and delta opioid receptors.

Emotionality vs. Other Biobehavioural Traits: A Look at Neurochemical Biomarkers for Their Differentiation

“…It has been shown that MOR (but not other ORs) agonists inhibit 5-hydroxytryptamine (serotonin) (5-HT) in the hippocampus (HC) (Yoshioka et al, 1993). In our experiments, when pregnant rats were chronically exposed to opium that caused downregulation of MOR receptors, they also had a significant decrease in endurance in four types of maternal behaviour, a decrease of 5-HT in HC, a decrease of BDNF and an increase of corticosterone (stress hormone) (Rezaei et al, 2021). Also, out of all OR, only MOR develop heteromeric complexes with the 5-HT1 receptors (Fujita et al, 2014).…”

“…The FC approach to bio-behavioural taxonomies was implemented in the neurochemical framework Functional Ensemble of Temperament (FET) that summarised the most conservative findings regarding the functionality of neurotransmitters, hormones, and OR systems (Trofimova, 2016(Trofimova, , 2018(Trofimova, , 2021aTrofimova and Robbins, 2016). The temperament of healthy individuals (including animals) and symptoms of psychiatric disorders can be presented as a continuum of weak vs. strong dysregulation within neurochemical systems generating CBPs (Sulis, 2018;Rezaei et al, 2021;Trofimova, 2021b). This conception of the continuum is supported by decades of research in psychopharmacology and neurochemistry, showing the impact of neurochemical dysregulation (Sulis, 2018).…”

Experience-Regulated Neuronal Signaling in Maternal Behavior

“…As CUS and other stress procedures are known to alter maternal behavior (Leuner et al, 2014 ; Maguire and Mody, 2016 ), it is probable that the reduction in Bdnf and FoxO1 might also be involved in these behavioral disturbances. Moreover, female rats exposed to opium during pregnancy showed reduced maternal behaviors in the postpartum period that were accompanied by decreased BDNF expression in the HPC (Rezaei et al, 2021 ). Supporting the hypothesis that activity-dependent events produced by bouts of maternal care involve BDNF, mothers that spent more time grooming and licking pups have higher levels of BDNF in the HPC and NAc (Zhang et al, 2020 ).…”

Functional Constructivism Approach to Multilevel Nature of Bio-Behavioral Diversity

“…There is a strong coupling between MOR and 5-HT systems. When pregnant rats were chronically exposed to opium that causes downregulation of MOR receptors, they also had significant decrease in endurance in four types of maternal behavior, a decrease of 5-HT in HC, a decrease of BDNF and an increase of corticosterone (stress hormones) ( 193 ). Out of all OR only MOR develop heteromeric complexes with 5-HT1 receptors ( 194 ).…”

“…This CBP includes low excitability about potential underachievement, no feeling of hopelessness or helplessness, severe problems with wanting, liking, planning and getting enthusiastic about anything, having remarkable stress resilience and full acceptance of who they are, in terms of social status. Chronic exposure to MOR stimulants affect 5-HT and BDNF systems causing a decrease in endurance ( 149 , 193 ). This, however, doesn't make people anxious about their low physical capacities, especially if there are supportive SEPs to accommodated their non-demanding lifestyle.…”