Systemic administration of thyrotropin-releasing hormone enhances striatal dopamine release in vivo

We examined the effects of systemically administered thyrotropin-releasing hormone (TRH) on the release of dopamine (DA), as assessed by brain microdialysis within the corpus striatum of anesthetized rats. A single dose (10 micrograms i.v.) elevated DA levels in brain extracellular fluid (ECF) by 240% above baseline levels after 150 min. Systemic tyrosine ([TME] 20 mg/kg i.v.) also increased DA release (by 190% after 150 min), while combined treatment with both agents was associated with significant potentiation of the DA response (to 640% after 150 min). None of the treatments significantly altered striatal tissue levels of DA or its metabolites. A large dose of TRH (50 micrograms i.v.) significantly increased DA release (by 1150%) whether or not animals had received an active or denatured prolactin (PRL) antiserum prior to the experiment, suggesting that the TRH effect is not mediated by PRL. Although TRH is rapidly metabolized in plasma and penetrates the blood-brain barrier only poorly, our results suggest that even relatively small doses of the hormone can affect striatal dopaminergic neurotransmission.