[beta-Phenylethylamine and amphetamine: similar aspects in their behavioropharmacological and neurochemical...

The authors found there was behavioral sensitization induced by repeated intermittent treatments with beta-phenylethylamine (PEA), an endogenous trace amine, similar to the so-called reverse-tolerance phenomenon which persists long after the withdrawal. A series of behavioropharmacological and neurochemical studies on the PEA-sensitized rats were compared with that on the sensitization induced by amphetamines (AMP). The major portion of this review focused on an involvement of dopaminergic modifications in the reverse tolerance caused by both PEA and AMP. The enhanced stereotype in the PEA-sensitized rats was found to be accompanied by augmentation of presynaptic dopaminergic activity in nigrostriatal and mesocorticolimbic systems by means of regional dissected and in vivo dialysis methods. In particular, a simultaneous measurement of endogenous PEA levels in striatum led us to speculate that the DA terminals in sensitized animals are hyperresponsive to PEA, resulting in enhanced DA release. D2 receptor bindings in nucleus accumbens, not in striatum, also altered in PEA-sensitized rats. In addition, recent literature concerning changes in PEA levels in body fluids in psychiatric disorders are summarized. Lastly, the attractive reports regarding the possibility that central actions of AMP would be mediated by endogenous PEA and that PEA is co-localized with DA in the same neurons were reviewed, suggesting an important role of endogenous PEA in generating the psychostimulant-induced and endogenous psychosis.