Abstract:
:Separate groups of rats were trained to discriminate either 0.1mg/kg (low dose; L) or 2.5mg/kg (high dose; H) of 8-OH-DPAT from saline, in a standard operant task. Both cues were found to be dose, time and route dependent and generalized completely to the 5-HT(1A) agonists ipsapirone and flesinoxan. Buspirone substituted completely for 8-OH-DPAT in L and partially in H, whereas the 5-HT(1A/1B) receptor agonist eltoprazine substituted completely for 8-OH-DPAT in H but only partially in L. The 5-HT(1A/1B) receptor agonist RU24969, the 5-HT(1B/2C/1A) receptor agonist TFMPP and the 5-HT reuptake blocker fluvoxamine did not completely mimic the effect of 8-OH-DPAT in either L or H and the 5-HT(1A) mixed agonists/antagonists BMY 7378 and NAN-190 produced partial generalization in L, but no generalization in H. In antagonism tests, NAN-190 and BMY 7378 only partially blocked the 8-OH-DPAT cue in both groups. The non-selective 5-HT receptor antagonist methysergide did not completely block the 8-OH-DPAT cue in in L or H. However, in generalization studies, it completely mimicked the 8-OH-DPAT cue in L and produced partial generalization in H. The beta-adrenergic/5-HT(1A/1B) receptor antagonist pindolol completely blocked the 8-OH-DPAT cue in L and H and did not mimic the 8-OH-DPAT cue in either condition. The alpha(2)-adrenoceptor blocker yohimbine substituted fully for the 8-OH-DPAT cue in L and partially in H. Idazoxan did not substitute for the cue of 8-OH-DPAT in H, but produced nearly 80% generalization in L. The dopamine receptor antagonist pimozide neither blocked nor mimicked the cue of 8-OH-DPAT in either group. A number of other drugs (i.e. m-CPP, S(-)-propranolol, DOI, ketanserin, clonidine and apomorphine) were only tested in H. S(-)-Propranolol blocked the 8-OH-DPAT cue but the other compounds produced neither stimulus generalization nor antagonism. The present study demonstrates that the cues produced by the low and the high training dose of 8-OH-DPAT are quantitatively different and mediated by the agonistic activity of 8-OH-DPAT at 5-HT(1A) receptors. Although the results suggest that the 8-OH-DPAT cue (both L and H) is mediated via postsynaptic 5-HT(1A) receptors, the involvement of presynaptic 5-HT(1A) receptors cannot yet be ruled out.
journal_name
Behav Pharmacoljournal_title
Behavioural pharmacologyauthors
Ybema CE,Slangen JL,Olivier B,Mos Jsubject
Has Abstractpub_date
1993-12-01 00:00:00pages
610-624issue
6eissn
0955-8810issn
1473-5849journal_volume
4pub_type
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journal_title:Behavioural pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-01-01 00:00:00
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journal_title:Behavioural pharmacology
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journal_title:Behavioural pharmacology
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journal_title:Behavioural pharmacology
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doi:10.1097/00008877-200311000-00005
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pub_type: 杂志文章,随机对照试验
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journal_title:Behavioural pharmacology
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更新日期:1992-10-01 00:00:00
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journal_title:Behavioural pharmacology
pub_type: 杂志文章
doi:10.1097/00008877-199102000-00010
更新日期:1991-02-01 00:00:00
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journal_title:Behavioural pharmacology
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doi:10.1097/00008877-200509000-00018
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pub_type: 杂志文章
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journal_title:Behavioural pharmacology
pub_type: 杂志文章
doi:10.1097/FBP.0b013e32835a3907
更新日期:2012-12-01 00:00:00
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journal_title:Behavioural pharmacology
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journal_title:Behavioural pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
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journal_title:Behavioural pharmacology
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doi:10.1097/00008877-199909000-00012
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journal_title:Behavioural pharmacology
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journal_title:Behavioural pharmacology
pub_type: 杂志文章
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更新日期:1995-04-01 00:00:00
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