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  • Title: Serotonin does not mediate anxiolytic effects of buspirone in the fear-potentiated startle paradigm: comparison with 8-OH-DPAT and ipsapirone.
    Author: Davis M, Cassella JV, Kehne JH.
    Journal: Psychopharmacology (Berl); 1988; 94(1):14-20. PubMed ID: 2894698.
    Abstract:
    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.
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