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

Elevated sensitivity to the euphoric or stimulant effects of ethanol is associated with higher levels of alcohol use in some human populations. Midbrain dopamine neurons are thought to be important mediators of both ethanol reward and locomotor stimulation. Patch-clamp recordings were used to examine the electrical properties of dopamine neurons in a genetic model of heightened (FAST) and reduced (SLOW) sensitivity to the locomotor-activating effects of ethanol. Pacemaker firing of dopamine neurons was faster in FAST than SLOW mice, as was the current density through I(H) channels. Acute administration of ethanol accelerated the firing of dopamine neurons to a greater extent in recordings from FAST than SLOW mice. Dopamine neurons from FAST mice also exhibited reduced GABA(A) receptor-mediated synaptic input, compared with SLOW mice. The results suggest that dopamine neuron I(H) channels, firing rate, and GABAergic input may play a role in sensitivity to the locomotor activation observed at early time points after ethanol administration and could underlie differences in sensitivity to alcohol relevant to risk for alcohol abuse.
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PMID:Mice selectively bred for high- or low-alcohol-induced locomotion exhibit differences in dopamine neuron function. 1912 13

Neuroanatomical research suggests that interactions between dopamine and glutamate within the mesolimbic dopamine system are involved in both drug-induced locomotor stimulation and addiction. Therefore, genetically determined differences in the locomotor responses to ethanol and cocaine may be related to differences in the effects of these drugs on this system. To test this, we measured drug-induced changes in dopamine and glutamate within the nucleus accumbens (NAcc), a major target of mesolimbic dopamine neurons, using in vivo microdialysis in selectively bred FAST and SLOW mouse lines, which were bred for extreme sensitivity (FAST) and insensitivity (SLOW) to the locomotor stimulant effects of ethanol. These mice also show a genetically correlated difference in stimulant response to cocaine (FAST > SLOW). Single injections of ethanol (2 g/kg) or cocaine (40 mg/kg) resulted in larger increases in dopamine within the NAcc in FAST compared with SLOW mice. There was no effect of either drug on NAcc glutamate levels. These experiments indicate that response of the mesolimbic dopamine system is genetically correlated with sensitivity to ethanol- and cocaine-induced locomotion. Because increased sensitivity to the stimulating effects of ethanol appears to be associated with greater risk for alcohol abuse, genetically determined differences in the mesolimbic dopamine response to ethanol may represent a critical underlying mechanism for increased genetic risk for alcoholism.
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PMID:Ethanol- and cocaine-induced locomotion are genetically related to increases in accumbal dopamine. 1922 Apr 81