Serotonin does not mediate anxiolytic effects of buspirone in the fear-potentiated startle paradigm: comparison with 8-OH-DPAT and ipsapirone.
The present study evaluated the role of various neurotransmitter systems in mediating buspirone's blockade of the fear-potentiated startle effect, where acoustic startle amplitude is normally increase in the presence of a light previously paired with a shock. Large lesions of the dorsal and median raphe nuclei or IP injections of the serotonin antagonists cinanserin (10 mg/kg) or cyproheptadine (5 mg/kg) did not alter fear-potentiated startle, nor did these treatments prevent buspirone (5 or 10 mg/kg SC) from blocking fear-potentiated startle. The 5-HT 1A agonist 8-OH-DPAT (2.5-10.0) did not block fear-potentiated startle even at doses that produced a marked "5-HT syndrome". Another 5-HT 1A agonist, ipsapirone (10-20 mg/kg), blocked potentiated startle only at a very high dose (40 mg/kg). p-Chlorophenylalanine and p-chloroamphetamine did not alter fear-potentiated startle. Finally, pretreatment with the benzodiazepine receptor antagonist RO-15-1788 (1 mg/kg); the opiate antagonist naloxone (2 mg/kg) or the alpha 2-adrenergic antagonist yohimbine (5 mg/kg) did not reduce fear-potentiated startle, nor did they prevent buspirone from blocking fear-potentiated startle. Taken together, the data do not support the hypothesis that buspirone's anxiolytic effects are mediated by actions at 5-HT 1A receptors and more generally indicate that serotonergic neurons do not play an important role in fear-potentiated startle.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000161:Acoustic Stimulation; D000818:Animals; D014151:Anti-Anxiety Agents; D002065:Buspirone / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D005239:Fear; D010134:Fenclonine / Q000494:pharmacology; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013216:Reflex, Startle / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D011743:Pyrimidines; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D012701:Serotonin; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010134:Fenclonine; D002065:Buspirone