D1 receptors function to inhibit the activation of tuberoinfundibular dopamine neurons

The effects of the D1 dopamine agonists SKF 38393 and CY 208-243 on the activity of tyrosine hydroxylase within tuberoinfundibular dopamine neurons were studied by measuring the accumulation of dihydroxyphenylalanine (DOPA) in the median eminence in vivo after inhibition of DOPA decarboxylase. SKF 38393 (5-20 mg/kg) and CY 208-243 (5-20 mg/kg) alone did not alter the accumulation of DOPA in the median eminence of male rats. However, the haloperidol-, reserpine- and neurotensin-induced increases in DOPA formation in the median eminence were antagonized dose-dependently by SKF 38393 (5-20 mg/kg i.p.) and/or CY 208-243 (5-20 mg/kg i.p.). Treatment of rats with SCH 23390 (0.5 mg/kg i.p.), a selective D1 antagonist, or loxapine (5 mg/kg i.p.), a dopamine antagonist with high affinity for D1 receptors, prevented the inhibitory effect of CY 208-243 on the haloperidol-induced activation of tyrosine hydroxylase in the median eminence. SKF 38393 did not inhibit the basal activity or the haloperidol-induced increase in activity of tyrosine hydroxylase in the striatum or nucleus accumbens. It is concluded that D1 receptor activation results in little or no effect on the basal rate of dopamine synthesis within tuberoinfundibular dopamine neurons, but under conditions in which the activity of tyrosine hydroxylase is increased D1 receptor stimulation results in a marked inhibition of the rate of dopamine synthesis within these neurons.