Reduction of in vivo striatal 5-hydroxytryptamine release by 8-OH-DPAT after inactivation of Gi/G(o) proteins in dorsal raphe nucleus.
5-HT1A receptor agonists reduce firing-dependent terminal 5-HT synthesis and release by activating somatodendritic 5-HT1A receptors. We have examined the effects of 8-hydroxy-2-(di-n- propylamino)tetralin (8-OH-DPAT, 0.1 mg/kg s.c.) on in vivo striatal 5-HT release in conscious rats with somatodendritic 5-HT1A receptors inactivated by the application of pertussis toxin in the dorsal raphe nucleus. The uncoupling of 5-HT1A receptors from hyperpolarizing potassium channels was demonstrated by the inability of the intra-raphe application of citalopram to reduce striatal release (control animals had a 47% reduction, an effect prevented by previous treatment with the 5-HT1A antagonist (-)-tertatolol). Yet 8-OH-DPAT (0.1 mg/kg s.c.) decreased striatal 5-HT release by 66% (peak effect) in pertussis toxin-treated rats, a value comparable to that found in naive animals (74%). This raises the possibility that other 8-OH-DPAT-sensitive serotonergic receptors different from 5-HT1A autoreceptors may be involved in the control of terminal 5-HT release.
Romero
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Department of Neurochemistry, CID, CSIC, Jordi Girona 18-26, Barcelona, Spain.
Celada
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Artigas
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D017660:Autoreceptors / Q000187:drug effects / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D037342:Pertussis Toxin; D015221:Potassium Channels / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D013876:Thiophenes; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D017660:Autoreceptors; D015221:Potassium Channels; D011412:Propanolamines; D013876:Thiophenes; D010566:Virulence Factors, Bordetella; D015283:Citalopram; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C005632:tertatolol; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins