3 (+)-PD 128907 inhibited cell firing in both the ventral tegmental area and substantia nigra pars compacta with EC50 values of 33 nM (pEC5o= 7.48+0.10, n = 10) and 38 nM (pEC50= 7.42+0.15, n = 5), respectively. No effects of (+)-PD 128907 (100 nM) were observed on glutamate or GABA-mediated synaptic potentials elicited by focal bipolar stimulation. 4 L-741,626 antagonized these effects of (+ )-PD 128907 in a concentration-dependent and surmountable manner with an affinity, determined from Schild analysis, of 20 nM (pKB= 7.71 + 0.14)in the ventral tegmental area and 11 nM (pKB = 7.95 + 0.18) in the substantia nigra pars compacta.5 (+)-PD128907 also inhibited dopamine release in the caudate-putamen with an ECso of 66 nM (n = 5). The affinity of L-741,626 for these nerve terminal autoreceptors (pKB= 7.71 + 0.06; = 20 nM) was identical to that observed on midbrain dopamine neurones. 6 These data demonstrate that the D3 receptor ligand (+)-PD 128907 is a potent agonist on rat midbrain dopamine neurones. However, its lack of regional selectivity, and the high affinity of the selective D2 receptor antagonist L-741,626 for receptors activated by (+ )-PD 128907, was more consistent with an action on D2 autoreceptors rather than upon a D3 dopamine receptor subtype.
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