Discriminative stimulus effects of apomorphine and 7-OH-DPAT: a potential role for dopamine D3 receptors.
Previous studies have reported that the non-selective dopamine agonist, apomorphine, can serve effectively as a discriminative stimulus in experimental animals, and evidence has been presented that this effect is mediated by dopamine D2 receptors. More recently, it has been found that another dopamine agonist, 7-OH-DPAT, which has some selectivity for D3 receptors, also produces a discriminative cue in rats. The present study set out to make a direct comparison of the discriminative stimulus effects of these two compounds. Rats were trained to discriminate either apomorphine (0.05 mg/kg, SC) or 7-OH-DPAT (0.1 mg/kg, IP) from saline. Both discriminations were acquired but extended training was necessary. Cross generalisation occurred between the two compounds and both cues generalised to the dopamine agonists, quinpirole, quinelorane, PD 128207, and bromocriptine. When the potencies of these compounds to produce the apomorphine or 7-OH-DPAT cues were correlated with their potencies to produce D2 or D3 functional responses in vitro (mitogenesis in transfected cells-results taken from the literature) stronger correlations with D3 than with D2 responses were observed. Both the cueing and the response rate-decreasing effects of apomorphine and 7-OH-DPAT were antagonised by the autoreceptor selective dopamine antagonist amisulpride, and sulpiride also antagonised the cues but without affecting response rates. In contrast, haloperidol blocked the cues but potentiated the response rate decreases. These results suggest that, at the doses used, apomorphine and 7-OH-DPAT produce similar discriminative stimuli, which may be mediated by presynaptically located dopamine D3 receptors.
Sanger
D J
DJ
Synthelabo Recherche, Bagneux, France.
Depoortere
R
R
Perrault
G
G
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D003216:Conditioning, Operant; D004193:Discrimination Learning; D018491:Dopamine Agonists / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D018491:Dopamine Agonists; C493595:Drd3 protein, rat; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D001058:Apomorphine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin