Title: Determination of the 5-HT receptor subtype involved in 8-OH-DPAT-induced hyperlocomotion: potential difficulties arising from inadequate pharmacological tools
Abstract: Selective 5-HT1A receptor agonists such as 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), flesinoxan, 5-methylurapidil and others, increased locomotor behaviour in rats following s.c. injection. Unfortunately, all available 5-HT1A receptor antagonists are non-selective, a fact which severely hampers their use. The inhibitory effects of (+)- and (-)-pindolol (1-10 mg/kg, -45 min s.c.) on locomotion induced by 8-OH-DPAT were investigated in rats pretreated with the beta-adrenoceptor antagonists, ICI 118,551 and betaxolol (both 1 mg/kg, -45 min s.c.). ICI 118,551 and betaxolol significantly enhanced the response to 8-OH-DPAT. Co-administration of (-)-pindolol (2-10 mg/kg) dose dependently antagonised the hyperlocomotion whereas (+)-pindolol was weakly effective at 10 mg/kg. The partial agonists ipsapirone (1-10 mg/kg, -45 min s.c.) and buspirone (0.1-1 mg/kg, -45 min) antagonised the effects of 8-OH-DPAT. This inhibition may, however, be due to alpha 1-adrenoceptor blockade and DA receptor antagonism, respectively. Finally, although spiroxatrine (0.1 and 1 mg/kg, -45 min s.c.) inhibited the response to 8-OH-DPAT, this inhibition may also be non-specific since spiroxatrine strongly reduced spontaneous locomotor activity. In conclusion, whilst much of our data is consistent with 8-OH-DPAT-induced locomotion being mediated by 5-HT1A receptors, only the data obtained with the pindolol enantiomers provide direct evidence for this. The results also suggest that, under normal circumstances, the 5-HT1A receptor antagonist effect of pindolol may be masked by the facilitating effect of beta-adrenoceptor blockade.
Publication Year: 1990
Publication Date: 1990-12-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 29
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