α-Conotoxin Bu1.3 (Bu1.3) was shown to be useful in differentiating norepinephrine release mediated by β2*-nAChRs in mice from β4*-nAChRs in rats (Azam et al., SFN, 2003). Here we have investigated the selectivity of Bu1.3 in differentiating β2*-nAChR mediated dopamine (DA) release from striatal synaptosomes of wildtype and nAChR subunit null mutant mice. In addition, the β4*-nAChR mediated acetylcholine release from wildtype mouse IPN was compared. Results show that 1) though competitive, Bu1.3, like α-conotoxin MII (MII), acts as a noncompetitive inhibitor because of slow off-rate kinetics. 2) Both α4 null mutant and α4β3 double null mutant mice have MII- and Bu1.3-sensitive DA release activity and no toxin resistant activity. 3) The onset of and recovery from Bu1.3 with β2*-nAChR-mediated DA release are faster than with MII. Onset and recovery from Bu1.3 are also measurably faster in wildtype mice than in α4 null mutant or α4β3 double null mutant mice. 4) IC50 values for inhibiting DA release from wildt...