Early exposure to environmental enrichment modulates the effects of prenatal ethanol exposure upon opioid gene expression and adolescent ethanol intake

Wille-Bille, Aranza; Bellia, Fabio; Garcı́a, Ana Maria; Miranda-Morales, Roberto Sebastián; Pautassi, Ricardo Marcos

doi:10.1016/j.neuropharm.2019.107917

Cited by 19 publications

(15 citation statements)

References 83 publications

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“…Further, control females exhibited a trend towards higher aggression compared to control males, a finding consistent with prior reports in zebrafish 63 . The increase in EtOH consumption in adult females as described in juvenile zebrafish 11 agrees with other reports in rats showing prenatal EtOH exposure to increase alcohol intake and preference in females more than males 35 , 40 , 64 . It is also consistent with clinical findings that females exposed in utero to low-moderate concentrations of EtOH are more susceptible than males to engage in problem drinking 65 and exhibit an increase in alcohol drinking during adolescence 8 and adulthood 66 .…”

Section: Discussionsupporting

confidence: 91%

“…There are only a few reports in any species examining both the brain and behavior at multiple stages of development 11 , 13 , and no studies of Hcrt neurons in adult subjects after embryonic EtOH exposure, only in young adolescent rats 35 and zebrafish 11 . With sex being a critically important biological variable for understanding the role of neuronal systems in controlling behavior and zebrafish rarely studied for their sex differences, we also expanded our analysis of adult subjects to include a direct comparison of female and male fish to determine if the stimulatory effects of embryonic EtOH exposure on Hcrt neurons and different behaviors are sexually dimorphic, perhaps stronger in females as shown in rats 35 , 40 .…”

Section: Introductionmentioning

confidence: 99%

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Sexually dimorphic and asymmetric effects of embryonic ethanol exposure on hypocretin/orexin neurons as related to behavioral changes in zebrafish

Collier

Yasmin

Khalizova

et al. 2021

Sci Rep

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Neurons expressing the neuropeptide hypocretin/orexin (Hcrt) in the hypothalamus promote reward-related behaviors including alcohol consumption and are shown in rodents and zebrafish to be stimulated by embryonic exposure to ethanol (EtOH). We used here in zebrafish three-dimensional analyses of the entire population of Hcrt neurons to examine how embryonic EtOH exposure at low-moderate concentrations (0.1% or 0.5% v/v) alters these neurons in relation to behavior. We found that EtOH in the water for 2 h (22–24 h post fertilization) increases the number of Hcrt neurons on the left but not right side of the brain through a stimulation of cell proliferation, this is accompanied by a decrease in locomotor activity under novel conditions but not after habituation, and these effects are evident in both larvae and adults indicating they are long lasting. Our analyses in adults revealed sexually dimorphic effects, with females consuming more EtOH-gelatin and exhibiting more freezing behavior along with an asymmetric increase in Hcrt neurons and males exhibiting increased aggression with no change in Hcrt. These findings suggest that a long lasting, asymmetric increase in Hcrt neurons induced by EtOH results from an asymmetric increase in proliferation specific to Hcrt and contributes to behavioral changes in females.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Sexually dimorphic and asymmetric effects of embryonic ethanol exposure on hypocretin/orexin neurons as related to behavioral changes in zebrafish

Collier

Yasmin

Khalizova

et al. 2021

Sci Rep

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“…On PD21 (see Figure 1A,B), the rats were housed in same-sex and same-line groups, 4 per cage (60 cm length × 40 cm width × 20 cm height cage), under SH or EE conditions (9,17,18). Rats in the EE group remained in a cage (60 cm length × 40 cm width × 40 cm height) that had two levels and seven objects, such as ladders, hollow cylinders, material to gnaw, a house-like object, and a running wheel.…”

Section: Rearing Conditions Across Pd21-42 (Experiments 1 and 2)mentioning

confidence: 99%

Environmental enrichment during adolescence heightens ethanol intake in female, but not male, adolescent rats that are selectively bred for high and low ethanol intake during adolescence

Suarez

Fabio

Bellia

et al. 2020

The American Journal of Drug and Alcohol Abuse

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Background: Discriminating between adolescents who will eventually have ethanol use problems from those who do not is important. Environmental enrichment is a promising approach to reduce drug-related problems, but its impact on ethanol's effects and intake is being scrutinized. Objective: We tested the effects of environmental enrichment on ethanol intake, preference, and anxiety-like response as well as shelter seeking and risk-taking behaviors. Methods: Experiment 1 examined ethanol intake, preference, and anxiety-like responses in 46 male and 54 female Wistar rats that were derived from a short-term breeding program that selected for high and low ethanol drinking during adolescence (ADHI 2 and ADLO 2 lines, respectively). Shelter-seeking and risktaking behaviors were assessed (Experiment 2) in ADHI 2 and ADLO 2 rats (73 males, 76 females) reared under environmental enrichment or standard housing conditions and given doses of ethanol (2.5 g/kg, intraperitoneal) for 3 weeks. Environmental enrichment was applied on postnatal days 21-42. Ethanol intake was measured on postnatal days 42-68. Anxiety-like behavior and exploratory responses were assessed using the light-dark box and multivariate concentric square field test. Results: In Experiment 1, environmental enrichment increased ethanol intake in female, but not male, ADHI 2 and ADLO 2 rats (p < 0.05). In the baseline measurement of Experiment 2, ADHI 2 rats exhibited reduced risk-taking and increased anxiety-like behavior (p < .05). After exposure to environmental enrichment the ADHI and ADLO rats, both males and females, exhibited increased risk-taking and exploratory behavior (p < 0.05). Conclusions: Environmental enrichment appears to increase ethanol intake in female rats by promoting the exploration of new environments or stimuli. The findings indicate that environmental enrichment increased ethanol intake in female, but not male, rats. Clinical programs that treat alcohol use disorder by emphasizing environmental stimulation should be designed with caution.

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“…Other preclinical studies have shown that environmental enrichment can ameliorate behavioral changes induced by perinatal exposure to other drugs of abuse, including nicotine, cocaine, morphine, ethanol, antiadrenergic, and antihypertensive drugs (44,46,(49)(50)(51)(52). These results suggest that enrichment may benefit infants and children with such exposures.…”

Section: Environmental Enrichment Effects On Behaviormentioning

confidence: 77%

Environmental enrichment mitigates the long-lasting sequelae of perinatal fentanyl exposure

Alipio

Riggs

Plank

et al. 2021

Preprint

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The opioid epidemic is a rapidly evolving societal issue that stems from the abuse of prescription and illicit opioids, including increasing use of synthetic opioids like fentanyl. Fentanyl use among women has increased substantially in the last decade, leading to a 40-fold increase in the number of perinatally-exposed infants. This exposure can result in neuropsychiatric abnormalities that persist into adolescence and, in some cases, adulthood. We previously developed a preclinical model to establish the consequences of perinatal fentanyl exposure and identified a pattern of synaptic pathophysiology that involves lasting impairments in primary somatosensory (S1) circuit function and behavior. Here, we ask if these long-lasting effects can be restored by a non-invasive intervention. We demonstrate that developmental exposure to environmental enrichment ameliorates many of fentanyl's deleterious behavioral effects, including hyperactivity, enhanced sensitivity to anxiogenic environments, and sensory maladaptation. As an extension of our past work, we found that perinatal fentanyl alters the frequency of miniature excitatory postsynaptic currents and impairs long-term potentiation in S1 layer 2/3 neurons. These deficits in synaptic function were restored by environmental enrichment. Environmental enrichment also affected neurons in control mice, reducing long-term potentiation and depression, and increasing frequency of miniature excitatory postsynaptic currents. These results demonstrate that the lasting somatosensory-related effects of fentanyl can be ameliorated with a non-invasive intervention introduced during early development. These findings can inform ongoing efforts to develop actionable steps toward mitigating the consequences of opioid abuse among pregnant women.

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Early exposure to environmental enrichment modulates the effects of prenatal ethanol exposure upon opioid gene expression and adolescent ethanol intake

Cited by 19 publications

References 83 publications

Sexually dimorphic and asymmetric effects of embryonic ethanol exposure on hypocretin/orexin neurons as related to behavioral changes in zebrafish

Sexually dimorphic and asymmetric effects of embryonic ethanol exposure on hypocretin/orexin neurons as related to behavioral changes in zebrafish

Environmental enrichment during adolescence heightens ethanol intake in female, but not male, adolescent rats that are selectively bred for high and low ethanol intake during adolescence

Environmental enrichment mitigates the long-lasting sequelae of perinatal fentanyl exposure

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