DOPAMINE TRANSPORTER-DEPENDENT AND TRANSPORTER-INDEPENDENT ENDOGENOUSDOPAMINE RELEASE FROM WEAVER MOUSE STRIATUM IN-VITRO

The weaver mutant mouse (wv/wv) has an similar to 70% loss of nigrostr iatal dopamine (DA) neurons, but the fractional DA release evoked by a mphetamine (but not a high potassium level) has been shown to be great er from striatal slices of the weaver compared with +/+ mice. In the p resent work we tested the hypothesis that fractional DA release from w eaver striatum would be greater when release was mediated by the DA tr ansporter. Serotonin (5-HT)-stimulated fractional DA release was great er from weaver than from +/+ striatum. The release evoked by 5-HT in t he presence of 10 mu M nomifensine (an antagonist of the DA transporte r) was less than in its absence, but the difference between weaver and +/+ striatum remained. In the presence of nomifensine, 1-(m-chlorophe nyl) biguanide, classified as a 5-HT, agonist, also induced a greater fractional release from weaver compared with +/+ striatum. When veratr idine was used at a low concentration (1 mu M), the fractional evoked release of DA was higher from the weaver in the presence and absence o f nomifensine. These findings suggest that the reason for the differen ce in the responsiveness of the two genotypes to these release-inducin g agents is not related to DA transporter function.