In vivo striatal dopamine release by TRH analog YM-14673 is blocked by M1 muscarinic receptor antagonist

A dialysis loop cannula was implanted into rat striatum under anesthetized conditions, and after 3 days surgical recovery the area was perfused with Ringer's solution, under freely moving conditions. Dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the serotonin metabolite, 5-hydroxyindoleacetic acid (5HIAA), recovered in the dialysate were measured by high-performance liquid chromatography with electrochemical detection. Thyrotropin-releasing hormone (TRH) and its analog YM-14673 were systemically administered. TRH (10 and 20 mg/kg) and YM-14673 (1 mg/kg) increased in vivo striatal DA, DOPAC, HVA and 5HIAA release. Treatment with YM-14673 increased DA, DOPAC, HVA and 5HIAA release to 145, 150, 155 and 125%, respectively, of basal levels. The effects of YM-14673 on DA release and metabolism were completely blocked by an M1 muscarinic receptor antagonist, pirenzepine (10(?5) M), perfused into the striatum through the dialysis membrane, and by pretreatment of an excitotoxin, kainic acid (2.5 ?g/2 ?l), microinjected directly into the striatum. In comparison with the case of DA, the effect of YM-14673 on the 5HIAA level was only slightly suppressed by pirenzepine and kainic acid. These results suggest that in vivo striatal DA release by TRH may be dependent upon the activation of cholinergic neurons.