COCAINE BEHAVIORAL SENSITIZATION AND THE EXCITATORY AMINO-ACIDS

Studies were conducted to identify neuroeffector systems involved in b ehavioral sensitization to cocaine-induced stereotypy in mice, and to compare the results with those from our previous amphetamine studies. The effects of eight relatively selective neuroeffector agonists and a ntagonists were measured in mice in order to identify specific functio nal changes associated with the sensitization. In contrast to amphetam ine, the only neuroeffector response altered by cocaine sensitization was a decrease in convulsive threshold to kainate. The persistence of the change in convulsive threshold correlated with the persistence of behavioral sensitization. The induction of sensitization was blocked b y pretreatment with four different classes of drugs, represented by ha loperidol, dizocilpine, diltiazem and DNQX. These results suggest that the mechanism of induction to cocaine is similar to that of amphetami ne; both the glutamate and dopaminergic systems appear to be involved in induction. The expression of the sensitized cocaine response was bl ocked by haloperidol, CPP and diltiazem. These results differed from t hose obtained previously insofar as CPP did not affect the expression of sensitization to amphetamine. Furthermore, DNQX, in contrast to its antagonism of the expression of amphetamine sensitization, did not af fect the expression of cocaine sensitization. The pharmacological data suggest that the mechanism of induction differs from that of expressi on, and that the mechanism of expression for cocaine sensitization dif fers from that for amphetamine.