Serotonin does not mediate anxiolytic effects of buspirone in the fear-potentiated startle paradigm: comparison with 8-OH-DPAT and ipsapirone

• Published in: Psychopharmacology Vol. 94; no. 1; p. 14
• Main Authors: Davis, M, Cassella, J V, Kehne, J H
• Format: Journal Article
• Language: English
• Published: Germany 01.01.1988
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin; Acoustic Stimulation; Animals; Anti-Anxiety Agents; Buspirone - pharmacology; Conditioning, Operant - drug effects; Fear; Fenclonine - pharmacology; Male; Pyrimidines - pharmacology; Raphe Nuclei - physiology; Rats; Rats, Inbred Strains; Reflex, Startle - drug effects; Serotonin - physiology; Serotonin Antagonists - pharmacology; Tetrahydronaphthalenes - pharmacology
• ISSN: 0033-3158
• DOI: 10.1007/BF00735873

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.