Discriminative stimulus effects of apomorphine and 7-OH-DPAT: a potential role for dopamine D3 receptors |
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Authors: | D J Sanger Ronan Depoortere Ghislaine Perrault |
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Institution: | (1) Synthelabo Recherche, 31 ave P. Vaillant-Couturier, F-92220 Bagneux, France Tel. (+33) 1/45362486, Fax (+33)1/45362070, FR |
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Abstract: | 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.
Received: 5 October 1996 / Final version: 15 November 1996 |
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Keywords: | Apomorphine 7-OH-DPAT Drug discrimination Dopamine D3 receptors |
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