Browsing by Subject "Locomotor sensitization"

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    Determining the heritability of ethanol-induced locomotor sensitization in mice using short-term behavioral selection
    (Springer, 2013-11) Linsenbardt, David N.; Boehm II, Stephen L.; Linsenbardt; Psychology, School of Science
    RATIONALE: Sensitization to the locomotor stimulant effects of alcohol (ethanol) is thought to be a heritable risk factor for the development of alcoholism that reflects progressive increases in the positive motivational effects of this substance. However, very little is known about the degree to which genes influence this complex behavioral phenomenon. OBJECTIVES: The primary goal of this work was to determine the heritability of ethanol-induced locomotor sensitization in mice using short-term behavioral selection. METHODS: Genetically heterogeneous C57BL/6J (B6) × DBA/2J (D2) F2 mice were generated from B6D2F1 progenitors, phenotyped for the expression of locomotor sensitization, and bred for high (HLS) and low (LLS) expression of this behavior. Selective breeding was conducted in two independently generated replicate sets to increase the confidence of our heritability estimates and for future correlated trait analyses. RESULTS: Large and significant differences in locomotor sensitization between HLS and LLS lines were evident by the fourth generation. Twenty-two percent of the observed line difference(s) were attributable to genes (h² = .22). Interestingly, locomotor activity in the absence of ethanol was genetically correlated with ethanol sensitization; high activity was associated with high sensitization. CONCLUSIONS: That changes in ethanol sensitivity following repeated exposures are genetically regulated highlights the relevance of studies aimed at determining how genes regulate susceptibility to ethanol-induced behavioral and neural adaptations. As alcohol use and abuse disorders develop following many repeated alcohol exposures, these data emphasize the need for future studies determining the genetic basis by which changes in response to alcohol occur.
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    Positive Allosteric Modulation of the GABAB Receptor by GS39783 Attenuates the Locomotor Stimulant Actions of Ethanol and Potentiates the Induction of Locomotor Sensitization
    (Elsevier, 2012) Kruse, Lauren C.; Linsenbardt, David N.; Boehm, Stephen L., II; Psychology, School of Science
    Acute ethanol-induced locomotor stimulation and ethanol-induced locomotor sensitization are two behavioral assays thought to model the rewarding effects of ethanol. Recent evidence suggests that GS39783, a GABA(B) positive allosteric modulator, may be effective at reducing both the rewarding and reinforcing effects of several drugs of abuse, including ethanol. The goal of this study was to determine if GS39783 was capable of altering acute ethanol-induced stimulation, and the induction and expression of ethanol-induced locomotor sensitization, without effecting basal locomotion levels. Several doses of GS39783 (ranging from 0 to 100 mg/kg, depending on experiment) were tested on adult male DBA/2J mice in four experiments using 3-day basal locomotion and acute ethanol stimulation paradigms, and 14-day induction and expression of ethanol sensitization paradigms. The results of experiment 1 are in agreement with current literature, suggesting that 30 mg/kg doses of GS39783 and lower do not alter basal locomotor activity. In experiment 2, we found that GS39783 significantly decreased acute ethanol stimulation, but only at the 30 mg/kg dose, supporting our hypothesis and other publications suggesting that GABA(B) receptors modulate acute ethanol stimulation. Contrary to our hypothesis, GS39783 did not alter the expression of locomotor sensitization. Additionally, repeated administration of GS39783 in conjunction with ethanol unexpectedly potentiated ethanol-induced locomotor sensitization. Further study of GS39783 is warranted as it may be a more tolerable treatment for alcoholism than full agonists, due to its behavioral efficacy at doses that lack sedative side effects. Our results add to current literature suggesting that the GABA(B) receptor system is indeed involved in the modulation of ethanol-induced locomotor stimulation and sensitization.