The D3 antagonist PNU-99194A potentiates the discriminative cue produced by the D3 agonist 7-OH-DPAT.
Based on correlations between potencies of various dopamine D2/D3 agonists to substitute for the 7-OH-DPAT discriminative cue and their in vitro (mitogenesis test) potencies, it has been suggested that the 7-OH-DPAT cue is mediated by activity at the D3 subtype. We sought to verify that the 7-OH-DPAT cue could be blocked by PNU-99194A, a commercially available preferential D3 antagonist. Rats were trained (FR10 two-lever, food-reinforced schedule) to press one lever following 7-OH-DPAT (0.1 mg/kg i.p.) and the other lever following saline. Rats were then tested with various doses of 7-OH-DPAT alone or in combination with PNU-99194A. 7-OH-DPAT (0.003 to 0.3 mg/kg) engendered dose-dependent substitution; PNU-99194A (1 to 10 mg/kg) failed to antagonize the cue induced by 0.1 mg/kg of 7-OH-DPAT and, at 10 mg/kg, given in combination with 0.003 to 0.1 mg/kg of 7-OH-DPAT, PNU-99194A markedly shifted the 7-OH-DPAT dose-effect curve to the left, i.e., potentiated the 7-OH-DPAT cue. If PNU-99194A is a preferential D3 antagonist, the present data do not confirm the previous hypothesis that the 7-OH-DPAT cue is mediated by the D3 subtype.
Depoortere
R
R
Synthélabo Recherche, Bagneux, France.
Perrault
G
G
Sanger
D J
DJ
D000818:Animals; D003463:Cues; D004193:Discrimination Learning / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007189:Indans / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493595:Drd3 protein, rat; D007189:Indans; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; C086335:(5,6-dimethoxyindan-2-yl)dipropylamine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin