Role of Genotype in the Development of Locomotor Sensitization to Alcohol in Adult and Adolescent Mice: Comparison of the DBA/2J and C57BL/6J Inbred Mouse … (original) (raw)
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Alcoholism: Clinical and Experimental Research, 1995
Investigations of ethanol's (EtOH's) complex response profile, including locomotor and other effects, are likely to lead to a more in-depth understanding of the constituents of alcohol addiction. Locomotor activity responses to acute and repeated EtOH (2 g/kg, ip) exposures were measured in BXD recombinant inbred (RI) mice and their C57BU6.J (B6) and DBN2J (D2) progenitors. Both the acute response and the change in initial EtOH response with repeated treatments were strain-dependent. The coefficient of genetic determination was 0.38-0.49 for initial locomotor response to EtOH, and 0.29 for change in response. Changes in response were largely attributable to sensitization of locomotor stimulation. Quantitative trait loci (QTL) analyses identified significant marker associations with basal activity, acute locomotor response, and change in response. Markers were for QTL on several chromosomes, and there was only one case of overlap in marker associations among phenotypes. Acute locomotor response and locomotor sensitization were negatively correlated with 3% EtOH preference drinking data collected in BXD RI strains. Overall, these results demonstrate locomotor sensitization induced by EtOH, suggest independence of genetic determination of locomotor responses to acute and repeated EtOH exposure, and partially support a relationship between reduced sensitivity to the locomotor stimulantlsensitizing effects of EtOH and EtOH consumption.
Sensitivity of inbred and selectively bred mice to ethanol
Alcohol, 1987
ALCOHOL 4(1) 57-62, 1987.-The Long-Sleep (LS) and Short-Sleep (SS) mice were bred for differences in sensitivity to ethanol as measured by duration of loss of the righting response (sleep time). The foundation population was a heterogeneous stock (HS) which was derived from a cross of eight inbred strains. Ethanol-induced sleep time and waking blood and brain ethanol levels were measured in the eight inbred strains, LS, SS and HS mice. The C3H and ISBI strains were quite resistant to ethanol as measured by sleep time, and only one, RIII, was very sensitive. Waking ethanol concentrations were similar for all of the inbreds, implying a narrow range of central nervous system sensitivity to ethanol. The HS mice had relatively short sleep times and blood ethanol levels equal to most of the inbreds. The LS mice were significantly more, and the SS mice significantly less sensitive to ethanol than any of the inbreds or HS mice. These studies suggest that the extremes of CNS sensitivities to ethanol manifested by the LS and SS mice cannot be traced to any of the inbred strains, and must have arisen through the selection process by changes in allelic frequencies of those genes conferring ethanol sensitivity and resistance. Long-Sleep mice Short-Sleep mice Inbred strains of mice Blood ethanol concentration Brain ethanol concentration Ethanol sleep time Acute tolerance
Ethanol-induced tolerance and sex-dependent sensitization in preweanling rats
Physiology & behavior, 2015
According to genetic studies, the acute stimulating effect of ethanol seems to be associated with an increased predisposition to consume large quantities of ethanol. Ethanol-induced stimulation has been rarely reported in adult rats. However, infant rats, particularly during the second postnatal week of life, are highly sensitive to ethanol-induced behavioral activation. They also consume more ethanol than in later ontogenetic stages. In adult mice repeated ethanol experience usually results in sensitization to the stimulating effect of ethanol, while tolerance is the predominant result in rats. The present study was designed to explore in rats whether repeated exposure to ethanol during infancy modifies subjects' sensitivity to the stimulating effect of the drug, either increasing or decreasing its magnitude (i.e. sensitization or tolerance, respectively). Furthermore, we also explored the possible context-modulation of these effects. In two experiments, subjects were trained w...
Psychopharmacology, 1991
Selectively bred FAST mice are highly susceptible, while SLOW mice are less susceptible, to the locomotor stimulant effects of ethanol. Heritability estimates indicate that approximately 15% of the variance in the FAST lines is of additive genetic origin, while low susceptibility is ostensibly nonheritable. Inbreeding has increased at the rate of 2 % per generation, but fertility has been unaffected. Measurement reliability for sensitivity to this ethanol effect was high when measured in both circular (r = 0.6) and square (r = 0.7) open-fields. In addition, our results indicate that we have selected for differences in sensitivity to ethanol rather than for differences in habituation to the test environment. The difference in response to ethanol between FAST and SLOW mice extended to tests varying in duration, and to a range of ethanol doses. We conclude that the divergence between FAST and SLOW mice generalizes to related test parameters, and speculate that the genetic architecture underlying the locomotor stimulant response may be simpler than previously proposed.
Differential Effects of Ethanol in Adolescent and Adult Rats
Alcoholism: Clinical and Experimental Research, 1996
Alcohol use in children and adolescents is widespread. However, very little is known about the effects of alcohol exposure during this period of postnatal development. The goal of the present study was to compare the relative sensitivity to the sedative effects of alcohol in periadolescent and adult rats. After treatment with either 4 or 5 glkg ethanol, both 20-and 30-day-old rats regained their righting reflex significantly earlier than 80-day old rats. In 30-day-old rats, serum ethanol concentrations (SECs) were significantly greater at the time of the recovety of the righting reflex than 80-day-old rats. Developmental differences in the effects of ethanol on locomotor activity were also observed. In 60-day-old rats, 2.5 glkg ethanol generally decreased locomotor activity. Ethanol did not significantly alter locomotor activity in 20-and 30-day-old rats. Finally, there were s i g nificant developmental differences in the pharmacokinetics of ethanol with a significant delay in the time to peak SECs in 80-day-old rats relative to 20-and 30-day-old rats. These findings indicate that periadolescent rats are less sensitive to the sedative effects of ethanol as they recovered their righting reflex earlier and at significantly higher SECs than adult rats.
Background: The low-dose stimulatory effect of ethanol (EtOH) in rats has been hypothesized to reflect its hedonic effects and to be associated with a genetic predisposition toward high alcohol preference. To test the hypothesis that phenotypes associated with high alcohol preference in adulthood are also present in adolescent rats at the time of onset of alcohol drinking, the current study examined the effects of EtOH on locomotor activity (LMA) during adolescence in lines of rats selectively bred for divergent alcohol intakes. Methods: Subjects were adolescent (31– 40 days of age) rats from the alcohol-preferring (P) and-nonpreferring (NP) lines and from the high–alcohol-drinking (HAD) and low–alcohol-drinking (LAD) replicate lines. On day 1, all subjects (n 8 –10/line/gender/dose) received intraperitoneal saline injections and were placed in the activity monitor for 30 min. On day 2, subjects received intraperitoneal saline or 0.25, 0.50, 0.75, 1.0, or 1.5 g EtOH/kg. Results: The LMA of male and female P rats was increased with low doses (0.25– 0.75 g/kg) and decreased at the highest dose (1.5 g/kg) of EtOH. Similar effects were observed with low doses of EtOH on the LMA of HAD-1 and HAD-2 rats. None of the EtOH doses stimulated LMA in the NP, LAD-1, or LAD-2 rats, although all of the low–alcohol-intake lines of rats showed decreased LMA at the highest dose of EtOH. Only the P rats among the high–alcohol-consuming lines of rats showed decreased LMA at the highest dose of EtOH. Conclusion: Selective breeding for high alcohol consumption seems to be associated with increased sensitivity to the low-dose stimulating effects of EtOH and reduced sensitivity to the high-dose motor-impairing effects of ethanol. The expression of these phenotypes emerges during adolescence by the age of onset of alcohol-drinking behavior.