SYSTEMIC ADMINISTRATION OF ATIPAMEZOLE, A SELECTIVE ANTAGONIST OF ALPHA-2-ADRENOCEPTORS, FACILITATES BEHAVIORAL ACTIVITY BUT DOES NOT INFLUENCE SHORT-TERM OR LONG-TERM-MEMORY IN TRIMETHYLTIN-INTOXICATED AND CONTROL RATS

The present study used trimethyltin (TMT)-intoxicated rats as a model for the behavioural syndrome seen after neuronal damage to the limbic system. Behavioural assessments indicated increased locomotor activity and reduced number of groomings in an open-arena task in TMT-intoxica ted (6.6 mg/kg as a free base) rats, as has been found previously. A n ovel finding was the severe deficit in swimming to a visible platform in the water maze task, with reduced swimming speed at the beginning o f the training period. During the reacquisition phase of a radial arm maze task, TMT-intoxicated rats made more short-term and long-term mem ory errors, and their behavioural activity was increased in comparison with controls. The administration of atipamezole (300 mu g/kg), a sel ective antagonist of alpha(2)-adrenoceptors, enhanced locomotor activi ty compared to saline-treated rats, but these effects did not differ b etween the TMT group and their controls. Atipamezole did not enhance s hea-term or long-term memory in either TMT or control groups. Taken to gether, the present data indicate that TMT intoxication is a model for global dementia rather than for a specific loss of relational memory. Previous studies on the neurochemical effects of TMT and the alleviat ion or prevention of neurotoxicity of TMT are reviewed. (C) 1998 Elsev ier Science Ltd. All rights reserved.