RT Journal Article
SR Electronic
T1 Enhanced Amphetamine- and K<sup>+</sup>-Mediated Dopamine Release  in Rat Striatum after Repeated Amphetamine: Differential Requirements for Ca<sup>2+</sup>- and Calmodulin-Dependent Phosphorylation and Synaptic Vesicles
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3801
OP 3808
DO 10.1523/JNEUROSCI.19-10-03801.1999
VO 19
IS 10
A1 Kantor, Lana
A1 Hewlett, G. H. Keikilani
A1 Gnegy, Margaret E.
YR 1999
UL http://www.jneurosci.org/content/19/10/3801.abstract
AB After cessation of repeated, intermittent amphetamine, we detected an emergent Ca2+-dependent component of amphetamine-induced dopamine release and an increase in calmodulin and Ca2+- and calmodulin-dependent protein kinase activity in rat striatum. This study examined the involvement of calmodulin-dependent protein kinase II (CaM kinase II) and synaptic vesicles in the enhanced Ca2+-dependent dopamine release in response to amphetamine or K+ in rat striatum. Rats were pretreated for 5 d with 2.5 mg/kg amphetamine or saline and withdrawn from drug for 10 d. The selective CaM kinase II inhibitor KN-93 (1 μm), but not the inactive analog KN-92, attenuated the Ca2+-dependent amphetamine-mediated dopamine release from amphetamine-pretreated rats but had no effect in saline-pretreated controls. [3H]Dopamine uptake was unaltered by repeated amphetamine or KN-93 and was Ca2+independent. Striatal dopamine release stimulated by 50 mmKCl was enhanced twofold after repeated amphetamine compared with that in saline controls but was unaffected by KN-93. To examine the requirement for dopaminergic vesicles in the Ca2+-dependent dopamine release, we administered reserpine to saline- and amphetamine-pretreated rats 1 d before killing. Reserpine pretreatment did not affect amphetamine-mediated dopamine release from either pretreatment group but completely ablated K+-mediated dopamine release. Reserpine did not disrupt the ability of 1 μm KN-93 to block the Ca2+-dependent amphetamine-mediated dopamine release from amphetamine-pretreated rats. The results indicate that the enhanced dopamine release elicited by amphetamine from chronically treated rats is dependent on Ca2+- and calmodulin-dependent phosphorylation and is independent of vesicular dopamine storage. On the contrary, the enhanced depolarization-mediated vesicular dopamine release is independent of Ca2+- and calmodulin-dependent phosphorylation.