Maternal Substance Use and Early-Life Adversity: Inducing Drug Dependence in Offspring, Interactions, Mechanisms, and Treatments.

The likelihood of substance dependency in offspring is increased in cases when there is a family history of drug or alcohol use. Mothering is limited by maternal addiction because of the separation. Maternal separation (MS) leads to the development of behavioural and neuropsychiatric issues in the future. Despite the importance of this issue, empirical investigations of the influences of maternal substance use and separation on substance use problems in offspring are limited, and studies that consider both effects are rare. This study aims to review a few studies on the mechanisms, treatments, genetics, epigenetics, molecular and psychological alterations, and neuroanatomical regions involved in the dependence of offspring who underwent maternal addiction and separation. The PubMed database was used. A total of 95 articles were found, including the most related ones in the review. The brain's lateral paragigantocellularis (LPGi), nucleus accumbens (NAc), caudate-putamen (CPu), prefrontal cortex (PFC), and hippocampus, can be affected by MS. Dopamine receptor subtype genes, alcohol biomarker minor allele, and preproenkephalin mRNA may be affected by alcohol or substance use disorders. After early-life adversity, histone acetylation in the hippocampus may be linked to brain-derived neurotrophic factor (BDNF) gene epigenetics and glucocorticoid receptors (GRs). The adverse early-life experiences differ in offspring>s genders and rewire the brain>s dopamine and endocannabinoid circuits, making offspring more susceptible to dependence. Related psychological factors rooted in early-life stress (ELS) and parental substance use disorder (SUD). Treatments include antidepressants, histone deacetylase inhibitors, lamotrigine, ketamine, choline, modafinil, methadone, dopamine, cannabinoid 1 receptor agonists/antagonists, vitamins, oxytocin, tetrahydrocannabinol, SR141716A, and dronabinol. Finally, the study emphasizes the need for multifaceted strategies to prevent these outcomes.

Chronic maternal morphine exposure and early-life adversity induce impairment in synaptic plasticity of adolescent male rats.

Maternal morphine exposure has negative consequences for learning and memory in the offspring. Interaction between mothers and pups has a crucial effect on the mammal's development. Maternal Separation (MS) can cause behavioral and neuropsychiatric problems later in life. It seems that adolescents are more susceptible to the effects of early life stress; evidence for the combinatory effects of oral chronic maternal morphine exposure and MS in the CA1 area of the hippocampus in the male adolescent offspring is not found. Therefore, this study aimed to evaluate the effects of chronic maternal morphine consumption (21 days before and after mating, and gestation), and MS (180 min/day from postnatal day (PND) 1-21) on the synaptic plasticity of male offspring in mid-adolescence. Control, MS, Vehicle (V), Morphine, V + MS, and Morphine + MS groups were tested for in vivo field potential recording from the CA1 area of the hippocampus. The current results demonstrated that chronic maternal morphine exposure impaired the induction of early long-term potentiation (LTP). MS impaired average fEPSPs, induction of early-LTP and maintenance. Chronic maternal morphine exposure in combination with MS impaired the induction of early LTP but didn't deteriorate maintenance and the average field excitatory post-synaptic potentials (fEPSPs) measured in two hours. Prepulse facilitation ratios remained undisturbed and I/O curves showed decreased fEPSP slopes at high stimulus intensities in combinatory group. We concluded that chronic maternal morphine exposure in combination with MS negatively affects synaptic plasticity in the CA1 area in male adolescent offspring.

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

Maternal morphine exposure reduces motivation for basic cognitive tasks, followed by executive function deficits in attention and accuracy. It also induces depression-like behaviors and has negative consequences for learning and memory in offspring. Interaction between mothers and pups has a crucial effect on the mammal's development. Maternal separation (MS) can originate behavioral and neuropsychiatric abnormalities later in life. It seems that adolescents are more susceptible to the effects of early-life stress; Therefore, this study aimed to evaluate the effects of chronic morphine consumption (21 days before and after mating and gestation) and MS (180 min/day from postnatal day [PND] 1-21) on the cognitive and behavioral performance of male offspring in mid-adolescence. Six groups, including control, MS, V (vehicle), morphine, V+MS, and morphine+MS, were tested for open field (OF), novel object recognition (NOR), and the Morris water maze (MWM). The results of the OF test showed that MS increased locomotor activity and movement velocity. Inner and outer zone durations did not differ among groups. The body stretching of the morphine+MS rats was significantly more than the MS rats. Moreover, the MS and morphine+MS groups showed significantly less sniffing behavior in the OF test. The MS group showed deficits in spatial learning in the MWM test, but recognition memory in the NOR and spatial memory in the MWM tests were not significantly different among groups. We concluded that MS could induce impairments in spatial learning and locomotor activity that could be worsened by maternal morphine exposure in adolescent male rats.