Dopamine transporter-dependent and -independent endogenous dopamine release from weaver mouse striatum in vitro

The weaver mutant mouse (wv/wv) has an approximately 70% loss of nigrostriatal dopamine (DA) neurons, but the fractional DA release evoked by amphetamine (but not a high potassium level) has been shown to be greater from striatal slices of the weaver compared with +/+ mice. In the present work we tested the hypothesis that fractional DA release from weaver striatum would be greater when release was mediated by the DA transporter. Serotonin (5-HT)-stimulated fractional DA release was greater from weaver than from +/+ striatum. The release evoked by 5-HT in the presence of 10 microM nomifensine (an antagonist of the DA transporter) was less than in its absence, but the difference between weaver and +/+ striatum remained. In the presence of nomifensine, 1-(m-chlorophenyl)biguanide, classified as a 5-HT3 agonist, also induced a greater fractional release from weaver compared with +/+ striatum. When veratridine was used at a low concentration (1 microM), the fractional evoked release of DA was higher from the weaver in the presence and absence of nomifensine. These findings suggest that the reason for the difference in the responsiveness of the two genotypes to these release-inducing agents is not related to DA transporter function.