β-Phenylethylamine Stimulates Striatal Acetylcholine Release through Activation of the AMPA Glutamatergic Pathway

Using an in vivo intra-striatal microdialysis technique, we examined the effects of systemically administered β-phenylethylamine (β-PEA), a psychomotor stimulating trace amine, on striatal acetylcholine release in freely moving rats. Infusion of N-methyl-D-aspartic acid (NMDA; 10−5 M) significantly increased acetylcholine release. In addition, locally applied amino-3-hydroxy-5-methylisozasole-4-propionic acid (AMPA; 10−5 M) significantly increased acetylcholine release in the striatum. Intra-striatal application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10−5 M), an AMPA-type glutamatergic receptor antagonist, had little effect on acetylcholine release, while application of MK-801 (10−5 M, 10−6 M), an NMDA-type glutamatergic receptor antagonist, significantly reduced acetylcholine release. Acetylcholine within striatal perfusate was significantly increased by intraperitoneal administration of β-PEA in a dose-dependent manner. This increase in acetylcholine release was completely blocked by application of CNQX (10−5 M) through the microdialysis probe into the striatum. However, increased acetylcholine response to systemic β-PEA was unaltered by addition of MK-801 to the perfusion medium. These results suggest a regulatory function of β-PEA, mediated by AMPA-type glutamatergic receptors, on the release of acetylcholine in the rat striatum.