Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.8 (FAST)
 758 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

FAST vs. SLOW selected mouse lines and C57BL/6J (B6) vs. DBA/2J (D2) inbred strains differ in their sensitivities to ethanol's locomotor stimulant effects, and provide two unique sets of genetic animal models to study neurophysiological substrates of this behavior. To determine whether NMDA receptor function mediates sensitivity to ethanol's stimulant effects, we assessed the effects of the noncompetitive NMDA antagonist, MK-801, on locomotor activity of naive and ethanol-treated FAST, SLOW, B6, and D2 mice. MK-801 (0.01-0.5 mg/kg, I.P.) had biphasic effects in all genotypes, with stimulation at moderate doses and decreased activation at the highest dose. FAST mice were more activated by MK-801 than SLOW mice, suggesting that selection differentially altered NMDA receptor function between the lines. B6 and D2 mice did not differ in locomotor responses following MK-801 administration. Stimulant doses of MK-801 decreased or blocked ethanol-stimulated locomotor activity in FAST and D2 mice, and potentiated the locomotor depressant actions of ethanol in SLOW and B6 mice. Potentiation of ethanol's activating properties was observed in one treatment group in D2 mice. These data suggest that NMDA receptors modulate ethanol's stimulant properties, by a more significant involvement in expression of ethanol's locomotor depressant properties.
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PMID:MK-801 potentiates ethanol's effects on locomotor activity in mice. 944 48

FAST and SLOW selected mouse lines were bred for differences in locomotor response to low-dose ethanol. FAST mice exhibit an extreme stimulant response and SLOW mice exhibit locomotor depression at the same ethanol dose. We tested the hypothesis that gamma-aminobutyric acid (GABA) systems modulate ethanol's stimulant effects by examining convulsant responses to GABAA receptor ligands, and by assessing the effects of GABAA and GABAB ligands on locomotor activity in the presence and absence of EtOH. FAST mice were more sensitive to the convulsant effects of GABAA drugs, and to one of two non-GABAergic drugs also tested. FAST and SLOW mice differed in locomotor responses to two benzodiazepines, but not to other GABAA receptor ligands. Ethanol's stimulant effects were not selectively altered by bicuculline or picrotoxin. The selected lines differed in sensitivity to the locomotor depressant effects of the GABAB agonist, baclofen. Ethanol-stimulated activity of FAST mice was inhibited by baclofen, and this effect was reversed by administration of the GABAB antagonist, CGP-35348. These GABAB receptor mediated effects were replicated in DBA/2J inbred mice that exhibit extreme sensitivity to ethanol's stimulant effects. In summary, we found moderate to strong evidence that some sites on the GABAA receptor complex were altered as a consequence of selection of FAST and SLOW mice, but found little support for GABAA mediation of EtOH-stimulated activity. In contrast, we found moderate evidence for differential alteration of GABAB receptor function; however, GABAB receptor involvement in ethanol-stimulated activity was strongly supported by results in the selected lines and an inbred strain.
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PMID:Seizure sensitivity and GABAergic modulation of ethanol sensitivity in selectively bred FAST and SLOW mouse lines. 980 87

The effect of ethanol on the number of Fos-like immunoreactive (Fos-li) neurons was previously studied in the C57BL/6J (B6) and DBA/2J (D2) inbred mouse strains (Hitzemann and Hitzemann, 1997). Data obtained suggested that the locomotor activation response to ethanol found in the D2 but not the B6 strain was associated with an increase in the number of Fos-li neurons (a putative measure of synaptic activity) in the central nucleus of the amygdala (CeA), but not in other brain regions, including the basal ganglia. Supporting results were obtained in B6D2 F2 intercross animals (Demarest et al., 1998) those animals exhibiting a marked locomotor activation response to ethanol also showed a significant increase in the number of Fos-li neurons in the CeA. The current study extends this line of investigation to the FAST and SLOW selected lines of mice (Shen et al., 1995). Twenty-eight SLOW and FAST mice (taken evenly from both replicate lines) were randomly assigned to receive either saline or ethanol (1.5 g/kg). One hour later, the animals were sacrificed, and the number of Fos-li neurons were determined using standard immunocytochemical techniques. Both the FAST and SLOW lines showed a marked increase (>300%) in the number of Fos-li neurons in the lateral aspect of the CeA; however, in the capsular division, only the FAST line showed an increase (>500%). In several brain regions, the basal (saline) response was markedly higher in the SLOW line; these regions included the subthalamic nucleus, the entopeduncular nucleus, the substantia nigra compacta, and the ventral tegmental area. Furthermore, it was found that ethanol decreased the number of Fos-li neurons in the ventral tegmental area of the SLOW but not FAST mice. These data suggest a substantial involvement of the basal ganglia in the segregation of the FAST and SLOW lines.
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PMID:Ethanol-induced expression of c-Fos differentiates the FAST and SLOW selected lines of mice. 1002 7