Biology subjects

Spear, L. P.

Publications and source records attributed to Spear, L. P..

4 recordsLinked to original sources

bioRxiv2021

IMPACT OF ADOLESCENT INTERMITTENT ETHANOL EXPOSURE IN MALE AND FEMALE RATS ON SOCIAL DRINKING AND NEUROPEPTIDE GENE EXPRESSION

BackgroundAlcohol use during adolescence can alter maturational changes that occur in brain regions associated with social and emotional responding. Our previous studies have shown that adult male, but not female rats demonstrate social anxiety-like alterations and enhanced sensitivity to ethanol-induced social facilitation following adolescent intermittent ethanol (AIE) exposure. These consequences of AIE may influence adult social drinking in a sex-specific manner. MethodsTo test effects of AIE on social drinking, male and female Sprague-Dawley rats exposed to water or ethanol [0 or 4 g/kg, intragastrically, every other day, between postnatal day (P) 25 and 45] were tested as adults (P72-83) in a social drinking paradigm (30-minute access to a 10% ethanol solution in supersac or supersac alone in groups of three same-sex littermates across two 4-day cycles separated by 4 days off). Social behavior was assessed during the last drinking session, with further assessment of oxytocin (OXT), oxytocin receptor (OXTR), vasopressin (AVP) and vasopressin receptors 1a and 1b (AVPR1a, AVPR1b) in the hypothalamus and lateral septum. ResultsMales exposed to AIE consumed more ethanol than water-exposed controls during the second drinking cycle, whereas AIE did not affect supersac intake in males. AIE-exposed females consumed less ethanol and more supersac than water-exposed controls. Water-exposed females drinking ethanol showed more social investigation as well as significantly higher hypothalamic OXTR, AVP, and AVPR1b gene expression than their counterparts ingesting supersac and AIE females drinking ethanol. In males, hypothalamic AVPR1b gene expression was affected by drinking solution, with significantly higher expression evident in males drinking ethanol than those consuming supersac. ConclusionsCollectively, these findings provide new evidence regarding sex-specific effects of AIE on social drinking and suggest that the hypothalamic OXT and AVP systems are implicated in the effects of ingested ethanol on social behavior in a sex- and adolescent exposure-dependent manner.

neuroscience↗

bioRxiv2020

Adolescent intermittent ethanol exposure effects on kappa opioid receptor mediated dopamine transmission: Sex and age of exposure matter

Underage alcohol drinking increases the risk of developing alcohol use disorder (AUD). In rodents, adolescent ethanol exposure augments ethanol consumption and anxiety-like behavior while reducing social interaction. However, the underlying mechanisms driving these adaptations are not understood. The dopamine and kappa opioid receptor (KOR) systems in the nucleus accumbens (NAc) are implicated in affective disorders and AUD, with studies showing augmented KOR function and reduced dopamine transmission in ethanol-dependent adult animals. Thus, this study, we examined the impact of adolescent intermittent ethanol (AIE) exposure on dopamine transmission and KOR function. Rats were exposed to water or ethanol (4 g/kg, intragastrically) every-other-day during early (PD25-45) or late (PD45-65) adolescence. While AIE exposure during early-mid adolescence (early AIE) did not alter dopamine release in male and female rats, AIE exposure during late adolescence (late AIE) resulted in greater dopamine release in males and lower dopamine release in females. To determine the impact of AIE exposure on KOR function, we bath applied cumulative concentrations of KOR agonist, U50,488 (0.01-1.0 M), and measured its effect on dopamine release. Early AIE exposure potentiated KOR-mediated inhibition of dopamine release in female rats, while late AIE exposure attenuated this effect in male rats. Together these data suggest that AIE-exposure impact on neural processes is dependent on sex and exposure timing. These differences likely arise from differential developmental timing in males and females. This is the first study to show changes in KOR function following AIE exposure.

neuroscience↗

bioRxiv2019

Critical Variables to be Considered when Attempting to Estimate Blood Ethanol Concentrations in Rats from g/kg Exposure Data

BackgroundIn rodent studies of ethanol (EtOH) consumption where blood sample collection does not occur, there is often mention of likely BECs based on prior studies. These studies may vary in dose(s) used, age/sex/species, or administration route. Often, intake studies may presume that binge-levels were achieved without knowing that BECs exceeded 80 mg% (binge threshold). In human studies, estimated BECs (eBECs) have been derived using complex formulas that consider EtOH consumption level and the weight and sex of the individual.\n\nMethodThree datasets were used to derive eBECs using a conversion factor (CF) that considers gram (g) of EtOH per kilogram (kg) of animal weight and other variables that may influence BECs such as age, sex, dose, route, vehicle, chronicity, and timing post-exposure. Regression analyses were also conducted for each dataset, building regression models with BEC as the response and other variables in the study specific to each dataset as predictor variables.\n\nResultsDataset1 assessed age, sex and post-injection time point. Both CF and regression analyses determined that different CFs should be used for 10- and 30-min post-administration time points. Dataset2 assessed age, dose, vehicle and post-intubation time point. Depending on the post-intubation time point, several CFs were used to derive eBECs. When weight was not used as a regression variable, data across approaches corresponded, with age differences emerging later in elimination phase. In Dataset3 that used BECs from a repeated intake study, chronic exposure influenced CFs, although regression analysis did not yield similar findings.\n\nConclusionsAlthough eBECs can be derived, critical variables vary with subject and test conditions and do not always concur with results of regression analyses. Although, not designed to replace assessment of BECs when sample collection is possible, the CF approach may prove useful when estimating BECs in studies where assessments are not feasible.

neuroscience↗

bioRxiv2018

Stress alters social behavior and sensitivity to pharmacological activation of kappa opioid receptors in an age-specific manner in Sprague Dawley rats

The dynorphin/kappa (DYN/KOR) system has been identified as a primary target of stress due to behavioral effects, such as dysphoria, aversion, and anxiety-like alterations that result from activation of this system. Numerous adaptations in the DYN/KOR system have also been identified in response to stress. However, whereas most studies examining the function of the DYN/KOR system have been conducted in adults, there is growing evidence suggesting that this system is ontogenetically regulated. Likewise, the outcome of exposure to stress also differs across ontogeny. Based on these developmental similarities, the objective of this study was to systematically test effects of a selective KOR agonist, U62066, on various aspects of social behavior across ontogeny in non-stressed male and female rats as well as in males and females with a prior history of repeated exposure to restraint (90 min/day, 5 exposures). We found that the social consequences of repeated restraint differed as a function of age: juvenile stress produced substantial increases in play fighting, whereas adolescent and adult stress resulted in decreases in social investigation and social preference. The KOR agonist U62066 dose-dependently reduced social behaviors in non-stressed adults, producing social avoidance at the highest dose tested, while younger animals displayed reduced sensitivity to this socially suppressing effect of U62066. Interestingly, in stressed animals, the socially suppressing effects of the KOR agonist were blunted at all ages, with juveniles and adolescents exhibiting increased social preference in response to certain doses of U62066. Taken together, these findings support the hypothesis that the DYN/KOR system changes with age and differentially responds and adapts to stress across development.

neuroscience↗