The purpose of this project is the investigation of basic mechanisms associated with naturally occurring or artifically neurotoxin-induced neurological disease through the use of animal models and in vitro experiments. Interactions of various neuroactive drugs and neurotoxins with neurotransmitters in the central nervous system have provided the focus for combined behavioral and neurochemical studies emphasizing basic mechanisms of action of proposed neurotoxins. Two major interests of this project are: (A) to define populations of individuals that may be at increased risk to neurological disease resulting from exposure to neurotoxins and (B) to use naturally occurring variability in central nervous system function, anatomy and/or neurochemistry, to elucidate mechanisms of actions of neurotoxins. Several different projects have been investigated this year. (1) Interactions of the artificial food color, erythrosin B, with neuronal membranes and neurotransmission have been studied. Erythrosin B has been demonstrated by several different criteria, to be a potent inhibitor of ATPase activity in brain and other tissues. Its inhibitory potency can be enhanced in vitro by exposing the tissue-erythrosin B complex to light. Our most recent data suggest that the light-enhanced inhibitory actions of erythrosin B may be a general phenomenon affecting a variety of excitable membranes but its dark phase inhibition may be specific to ATPAses. (2) We have been investigating an apparently new neurological mutation in rat discovered in our animal breeding unit. Animals display a form of ataxia which appears to be inherited in the pattern characteristic of single gene autosomal traits. Preliminary neuroanatomical studies have discovered some axonal degeneration in the cortical fugal and limbic systems. (3) For several years we have been studying the effects of convulsants and anticonvulsants on adenosine receptors in rat brain. Carbamazepine, a clinically used anticonvulsant, was found to have a major inhibitory action on brain adenosine receptors. We have been unable, however, to classify it as either a pure agonist or antagonist at A1 adenosine receptors.
