Student’s two-tailed t tests were used to compare unpaired data between two groups

presence of high-dose AMPH: increase, no change, and decrease for short, intermediate, and long trains, respectively. Taken together, these results suggest that AMPH purchase Vatalanib augments the readily releasable pool, exerts no effect on the recycling pool, and depletes the reserve pool in the dorsal striatum. By contrast, the readily releasable pool and to a lesser extent the recycling pool were upregulated without depletion of the reserve pool by AMPH in the ventral striatum and cocaine in both striatal sub-regions. As a psychostimulant with multiple actions, AMPH could augment vesicular dopamine release by several mechanisms, such as: inhibiting monoamine oxidase and activating tyrosine hydroxylase, leading to greater cytosolic dopamine levels, vesicular packaging, and ultimately quantal size; increasing membrane excitability as a DAT substrate; and enhancing exocytosis by liberating vesicular Ca2+ stores. Depleting the reserve pool suggests another mechanism, re-distributed cytosolic dopamine being re-packaged by the readily releasable pool. This latter postulate is supported by the greater capacity of this 22172704 vesicle population to sequester cytosolic dopamine. Moreover, robust depletion of vesicular dopamine stores by AMPH, well established using reduced preparations, appears to occur independently in separate classes of dopamine vesicles. Depletion involves AMPH acting as a 15120495 weak base to destabilize the proton gradient across vesicles and as a substrate of the vesicular monoamine transporter to inhibit and/or reverse its action. How these mechanisms might differ across dopamine storage pools, as our results would suggest, remains to be determined. We also do not know why AMPH depleted vesicular dopamine stores in the dorsal but not ventral striatum. One possible origin is regional differences in DAT. For example, DAT binding and Vmax for dopamine uptake are higher in the dorsal striatum, and DAT is more glycosylated with a higher molecular weight in the ventral striatum. Although Km for dopamine uptake is similar in the two regions, AMPH is a more potent competitive inhibitor of dopamine uptake in the dorsal compared to the ventral straitum. We are not aware of comparable regional differences in the vesicular monoamine transporter. Another possible origin is regional differences in vesicular dopamine stores. As mentioned above, different classes of dopamine vesicles exhibit different sensitivities to the depleting actions of AMPH. Consistent with region-specific actions of AMPH on vesicular dopamine stores, we have recently shown that AMPH may upregulate vesicular dopamine release in the ventral striatum by mobilizing the reserve pool but by activating dopamine synthesis and inhibiting dopamine degradation in the dorsal striatum. Different distributions of small, clear and large, dense-core vesicles in the two striatal sub-regions may also contribute to the differential response to AMPH. Clearly, more work needs to be Stimulus-dependent effects of AMPH on max The present results, obtained by applying different train durations to the same animal, are consistent with previous work applying these same trains individually in separate animals. For example, in the presence of AMPH and in the dorsal striatum, the long train decreased max, the intermediate train elicited minimal to no effect, and the short train increased max. Similar results were obtained in the ventral striatum, except that the long train did not decrease max, which is also consistent w