Neurotoxicology and teratology
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Neurotoxicol Teratol · Sep 2012
Investigation of calcium-stimulated adenylyl cyclases 1 and 8 on toluene and ethanol neurobehavioral actions.
The abused inhalant toluene has potent behavioral effects, but only recently has progress been made in understanding the molecular pathways that mediate the action of toluene in the brain. Toluene and ethanol induce similar behavioral effects and share some targets including NMDA and GABA receptors. In studies examining neuronal actions of ethanol, mice lacking the calcium-stimulated adenylyl cyclases (ACs), AC1 and AC8 (DKO), show increased sedation durations and impaired protein kinase A (PKA) phosphorylation following acute ethanol treatment. ⋯ In WT mice, both doses of ethanol increased distance traveled compared to saline controls. Conversely, DKO mice demonstrated no increase in locomotor activation at 1.0g/kg, with significantly reduced distances traveled at both doses compared to ethanol-treated WT mice. These behavioral activity results suggest that acute effects of ethanol and toluene are distinct in the mechanisms by which they induce acute sedating effects with respect to AC1 and AC8 activity, but may be similar in the mechanisms subserving locomotor stimulation.