AMPHETAMINE INDUCES EXCESS RELEASE OF STRIATAL ACETYLCHOLINE IN-VIVO THAT IS INDEPENDENT OF NIGROSTRIATAL DOPAMINE

The effect of amphetamine on striatal acetylcholine (ACh) release was studied by an in vivo intrastriatal microdialysis technique. Although we expected systemic amphetamine to inhibit baseline striatal ACh rele ase, the opposite was found. In addition, we found that the amphetamin e-induced striatal ACh release did not depend on nigrostriatal DA sinc e 6-hydroxydopamine (6-OHDA) lesions had no effect on amphetamine-indu ced ACh release. Local intrastriatal injection of amphetamine via the microdialysis probe had no effect on striatal ACh release even when th e probe was located more laterally in striatum to take advantage of th e medial to lateral gradient of striatal ACh and D-2 receptors. The hy pothesis that amphetamine increased extracellular striatal ACh by incr easing the release of biogenic amines besides dopamine was tested by p harmacological manipulations designed to specifically increase local s triatal norepinephrine or serotonin levels. The serotonergic and norad renergic manipulations had no effect on striatal ACh levels. These res ults indicate that amphetamine-induced release of ACh in striatum is m ediated via distal brain regions that are functionally connected with the striatum.