Exogenous tyrosine potentiates the methylphenidate-induced increase in extracellular dopamine in the nucleus accumbens: a microdialysis study.

Previous work has shown that the synthesis and release of dopamine may, under certain conditions, be influenced by an increase in the availability of its amino acid precursor, tyrosine. To examine whether exogenous tyrosine could potentiate the methylphenidate-induced increase in extracellular dopamine, male rats were implanted with microdialysis probes aimed at the right nucleus accumbens. Samples were collected from awake animals beginning 22 h after surgery. A repeated measures design was used involving the continuous collection of 20-min samples for a 4-h period once a day for 3 consecutive days. On a given day, an animal was infused with methylphenidate, tyrosine, or methylphenidate plus tyrosine. Periods of infusion with the active compounds were preceded and followed by baseline conditions, and treatments were counterbalanced to control for possible order effects. Methylphenidate plus tyrosine significantly increased extracellular levels of dopamine in comparison to drug alone. This effect was long-lasting, persisting into the post-treatment sampling period and peaking 40 min after the peak induced by methylphenidate alone. Tyrosine alone induced a small but significant increase in extracellular dopamine in the absence of any treatment to accelerate the firing of dopamine cells. These findings may have implications for the treatment of attention deficit hyperactivity disorder.