Determination of the 5-HT receptor subtype involved in 8-OH-DPAT-induced hyperlocomotion: potential difficulties arising from inadequate pharmacological tools

Hans O. Kalkman*, Jasmeet Soar

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

29 Citations (Scopus)


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 β-adrenoceptor antagonists, ICI 118,551 and betaxolol (both l 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 α1-adrenoceptor blockade and DA receptor antagonism, respectively. Finally, although spiroxatrine (0.1 and l 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 β-adrenoceptor blockade.

Original languageEnglish
Pages (from-to)383-390
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number3
Publication statusPublished - 4 Dec 1990

Bibliographical note

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  • 5-HT receptors
  • Dopamine receptors
  • Locomotion
  • α-Adrenoceptor antagonists
  • β-Adrenoceptor antagonists

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