Noradrenergic neurotransmission in the brain of a convulsive mutant mouse, differences between the cerebral cortex and the brain stem.
The Quaking mouse is a genetically determined model of convulsive disorders. We investigated the modulation of noradrenergic neurotransmission through alpha 2-adrenoceptors in the occipital cortex and the brain stem of this mutant. The endogenous levels of noradrenaline were similar in the cerebral cortex of the Quaking mice and their corresponding controls, while a significant increase of endogenous noradrenaline was found in the brain stem of the mutants. The rate of disappearance of noradrenaline in the cerebral cortex and the brain stem after injection of FLA 63 was identical in control and Quaking mice. The calcium-dependent electrically evoked overflow of 3H-noradrenaline from slices of occipital cortex was inhibited by clonidine and enhanced by yohimbine in Quaking as well as in normal mice. The negative feed-back mechanism mediated by presynaptic alpha 2-adrenoceptors operates to a similar extent in both strains of mice. In contrast to the occipital cortex, in the brain stem, the amount of neurotransmitter released by electrical stimulation was significantly increased in Quaking mice when compared with controls. However, in the brain stem, the negative feed-back regulation of noradrenaline release operates to a similar extent in both strains of mice. When the endogenous levels of MOPEG were determined in the brain stem, they were found to be significantly higher in the Quaking mice when compared to the controls. The results suggest that an increase in noradrenergic neurotransmission in the brain stem, rather than in the cerebral cortex, could contribute to the behavioural abnormalities exhibited by the Quaking mice.
D000818:Animals; D001921:Brain / Q000378:metabolism; D001933:Brain Stem / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008821:Mice, Quaking; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*; D012640:Seizures / Q000503:physiopathology*; D009435:Synaptic Transmission; D015016:Yohimbine / Q000494:pharmacology
D015016:Yohimbine; D003000:Clonidine; D009638:Norepinephrine