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Environmental Enrichment During Adolescence Mitigates Cognitive Deficits and Alcohol Vulnerability due to Continuous and Intermittent Perinatal Alcohol Exposure in Adult Rats.

ABSTRACT: Perinatal alcohol exposure affects ontogenic neurodevelopment, causing physical and functional long-term abnormalities with limited treatment options. This study investigated long-term consequences of continuous and intermittent maternal alcohol drinking on behavioral readouts of cognitive function and alcohol vulnerability in the offspring. The effects of environmental enrichment (EE) during adolescence were also evaluated. Female rats underwent continuous alcohol drinking (CAD)-or intermittent alcohol drinking paradigm (IAD), along pregestation, gestation, and lactation periods-equivalent to the whole gestational period in humans. Male offspring were reared in standard conditions or EE until adulthood and were then assessed for declarative memory in the novel object recognition test; spatial learning, cognitive flexibility, and reference memory in the Morris water maze (MWM); alcohol consumption and relapse by a two-bottle choice paradigm. Our data show that perinatal CAD decreased locomotor activity, exploratory behavior, and declarative memory with respect to controls, whereas perinatal IAD displayed impaired declarative memory and spatial learning and memory. Moreover, both perinatal alcohol-exposed offspring showed higher vulnerability to alcohol consummatory behavior than controls, albeit perinatal IAD rats showed a greater alcohol consumption and relapse behavior with respect to perinatal-CAD progeny. EE ameliorated declarative memory in perinatal CAD, while it mitigated spatial learning and reference memory impairment in perinatal-IAD progeny. In addition, EE decreased vulnerability to alcohol in both control and perinatal alcohol-exposed rats. Maternal alcohol consumption produces drinking pattern-related long-term consequences on cognition and vulnerability to alcohol in the offspring. However, increased positive environmental stimuli during adolescence may curtail the detrimental effects of developmental alcohol exposure.

SUBMITTER: Brancato A

PROVIDER: S-EPMC7546794 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Environmental Enrichment During Adolescence Mitigates Cognitive Deficits and Alcohol Vulnerability due to Continuous and Intermittent Perinatal Alcohol Exposure in Adult Rats.

Brancato Anna A Castelli Valentina V Lavanco Gianluca G Cannizzaro Carla C

Frontiers in behavioral neuroscience 20200925

Perinatal alcohol exposure affects ontogenic neurodevelopment, causing physical and functional long-term abnormalities with limited treatment options. This study investigated long-term consequences of continuous and intermittent maternal alcohol drinking on behavioral readouts of cognitive function and alcohol vulnerability in the offspring. The effects of environmental enrichment (EE) during adolescence were also evaluated. Female rats underwent continuous alcohol drinking (CAD)-or intermittent ...[more]

PMID: 33100982

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Project description:BackgroundCastration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence.MethodsMen with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and a prostate-specific antigen (PSA) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an antiandrogen agent for 7 months. We then randomly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent androgen deprivation, with patients stratified according to prior or no prior hormonal therapy, performance status, and extent of disease (minimal or extensive). The coprimary objectives were to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival, with a one-sided test with an upper boundary of the hazard ratio of 1.20, and whether quality of life differed between the groups 3 months after randomization.ResultsA total of 3040 patients were enrolled, of whom 1535 were included in the analysis: 765 randomly assigned to continuous androgen deprivation and 770 assigned to intermittent androgen deprivation. The median follow-up period was 9.8 years. Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group (hazard ratio for death with intermittent therapy, 1.10; 90% confidence interval, 0.99 to 1.23). Intermittent therapy was associated with better erectile function and mental health (P<0.001 and P=0.003, respectively) at month 3 but not thereafter. There were no significant differences between the groups in the number of treatment-related high-grade adverse events.ConclusionsOur findings were statistically inconclusive. In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that we cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy. Intermittent therapy resulted in small improvements in quality of life. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00002651.).

Dataset Information

Environmental Enrichment During Adolescence Mitigates Cognitive Deficits and Alcohol Vulnerability due to Continuous and Intermittent Perinatal Alcohol Exposure in Adult Rats.

Publications

Environmental Enrichment During Adolescence Mitigates Cognitive Deficits and Alcohol Vulnerability due to Continuous and Intermittent Perinatal Alcohol Exposure in Adult Rats.

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