Comparative behavioral sensitization to stereotypy by direct and indirect dopamine agonists in CF-1 mice

The present experiments were designed to compare the properties of behavioral sensitization induced by the indirect agonists, amphetamine and cocaine, to that induced by the direct dopamine agonists, apomorphine and PPHT. Both classes of agonist produced sensitization when administered either in relatively low daily doses or in a single high dose. Mice sensitized to the indirect agonists were cross-sensitized to the direct agonists and vice versa. A pharmacological evaluation of the sensitization induced by the two types of agonist demonstrated both similarities and dissimilarities. Induction to the indirect agonists is blocked by CPP, DNQX and diltiazem, whereas only CPP and diltiazem blocked induction to the direct agonists. Furthermore, although none of these antagonists block the expression of sensitization by the direct agonists, all three were previously shown to block the amphetamine expression of sensitization. Striking differences were also observed in the persistence of the sensitization induced by the two types of agonists. While the indirect agonist-induced sensitization is long lasting, the direct agonist-induced sensitization is relatively short-lived. Furthermore, cross-sensitization of PPHT in amphetamine-sensitized animals was also short-lived, as was amphetamine cross-sensitization in PPHT-sensitized animals. The data suggest that the induction of sensitization consists of two separable mechanisms, one for induction per se, the other for persistence.