The effects of some neuroleptics and d-amphetamine on striatal 2-phenylethylamine in the mouse

1. Mouse striatal 2-phenylethylamine was not changed at 2 hr following the administration of chlorpromazine, fluphenazine or spiperone. 2. In contrast, when the mice were first given pargyline (2 mg kg-1), treated with chlorpromazine, fluphenazine or spiperone 2 hr later and killed at 4 hr, a significant increase (to 130-170%) in the accumulation of 2-phenylethylamine was observed with respect to the pargyline controls. 3. The effect of chlorpromazine was consistently observed after pretreatment with either deprenyl (2 mg kg -1) or high doses (200 mg kg-1) of pargyline that produced different degrees of MAO inhibition. 4. Following pretreatment with pargyline (2 mg kg-1), d-amphetamine (5 mg kg-1) produced a significant reduction in striatal 2-phenylethylamine concentrations (to 39% of pargyline-treated controls). 5. The findings show that inhibition of dopamine transmission by neuroleptics increases the rate of 2-phenylethylamine accumulation. 6. Conversely, a stimulation of dopamine transmission by d-amphetamine results in a reduction in the rate of accumulation of 2-phenylethylamine and supports the concept of 2-phenylethylamine may be a neuromodulator of dopamine transmission.