Central adrenergic receptor changes in the inherited noradrenergic hyperinnervated mutant mouse tottering

Adrenergic receptor binding characteristics were analyzed in the mutant mouse tottering (tg/tg), a single gene locus autosomal recessive mutation causing hyperinnervation by locus coeruleus neurons of their target regions, which results in epilepsy. Instead of the expected down-regulation of receptors due to the hyperinnervation, both [3H]prazosin (alpha 1-receptor) and [125I]iodopindolol (beta-receptor) binding were normal in the tg/tg hippocampus, spinal cord and slightly increased in the cerebellum. This lack of postsynaptic receptor modulation in the target cells, combined with increased levels of norepinephrine due to the aberrant axon growth, may the critical factors in the expression of the abnormal spike-wave absence seizures in the tg/tg mouse.