Comparison between the pharmacology of dopamine receptors mediating the inhibition of cell firing in rat brain slices through the substantia nigra pars compacta and ventral tegmental area.

摘要

1. Electrophysiological recordings were made from presumed dopaminergic neurons in the substantia nigra pars compacta and ventral tegmental area of rat brain slices. The ability of selective dopamine receptor agonists to hyperpolarize neurones and inhibit cell firing, as well as the ability of dopamine receptor antagonists to block responses to quinpirole were compared. 2. Six dopamine receptor agonists were examined for their ability to hyperpolarize neurones within the substantia nigra pars compacta. Of these, the most potent ligand tested was naxagolide with an EC50 value of 20 nM and estimated maximum of 10 mV. The rank order of agonist potency was naxagolide > quinpirole > apomorphine > dopamine. 3. Quinpirole was more potent at inhibiting cell firing in the substantia nigra pars compacta (pIC50 = 7.65 +/ 0.06, n = 35) than in the ventral tegmental area (pIC50 = 7.24 +/- 0.06, n = 32; P < 0.01, Student's t test). 7-Hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT), a putative D3 selective agonist, had a comparable potency to quinpirole in both the ventral tegmental area (pIC50 = 7.39 +/- 0.26, n = 4), and substantia nigra pars compacta (pIC50 = 7.71 +/- 0.20; n = 4). 4. The inhibition of cell firing by quinpirole was antagonized by haloperidol, S(-)-sulpiride, clozapine, and ritanserin. S(-)-sulpiride and haloperidol had the highest estimated affinities in the substantia nigra, with pA2 values of 8.97 (slope = 0.85) and 8.20 (slope = 2.09) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)