The role of 5HT1A receptors in the modulation of the acoustic startle reflex in rats.
The modulatory role of serotonin (5-HT) on the acoustic startle reflex was studied using 5-HT receptor agonists and antagonists. 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT) (1,2 and 4 mg/kg, SC) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (1,2 and 4 mg/kg, IP), putative 5-HT1a receptor agonists, increased the magnitude of the startle reflex, while quipazine (5, 10 and 20 mg/kg, SC), an agonist with mixed 5-HT2 and 5-HT1b receptor activity, decreased startle responsiveness. Pretreatment of rats with ketanserin (1, 2 and 4 mg/kg, SC), a 5-HT2 receptor antagonist, had no significant effect on the activity of 8-OHDPAT, 5-MeODMT, or quipazine. Metergoline (0.25, 0.5, 1 and 2 mg/kg, SC), a mixed 5-HT1/5-HT2 receptor antagonist attenuated the augmentation of the reflex by 8-OHDPAT and 5-MeODMT and the suppression produced by quipazine. At the doses used, metergoline produced a non-dose-dependent increase in startle, while ketanserin had no effect. None of the agents specifically affected the ability of a prepulse stimulus to inhibit the acoustic startle response. These data suggest that 5-HT1a and 5-HT1b receptors play opposite roles in the modulation of the acoustic startle response and that 5-HT plays little, if any, role in the prepulse inhibition of the acoustic startle response.
Nanry
K P
KP
Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Tilson
H A
HA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000161:Acoustic Stimulation; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011985:Receptors, Serotonin / Q000502:physiology*; D013216:Reflex, Startle / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D008732:Methoxydimethyltryptamines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D008711:Metergoline; D011814:Quipazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin