Serotonergic modulation of the acoustic startle response in rats during preweaning development.
The involvement of serotonin (5-HT) in modulating the acoustic startle response (ASR) is well established in adult rats, but 5-HT involvement during the preweaning period, when 5-HT neurons undergo extensive development, has not previously been described. Three 5-HT receptor subtypes are reported to modulate the ASR in adult rats: 5-HT1A and 5-HT2 receptor agonists facilitate the ASR, whereas 5-HT1B agonists decrease the response. In the present study, the effects of 5-HT agonists and generalized 5-HT depletion on the ASR were studied in preweanling animals, using independent groups of Long-Evans rats tested on postnatal day (PND) 13, 17 and 21. 8-Hydroxy-2-(di-n-propylamino) tetralin (8OHDPAT, 62-1000 micrograms/kg), a 5-HT1A receptor agonist, and 5-methoxy-N,N-dimethyl tryptamine (MeODMT, 2-4 mg/kg), a nonselective 5-HT agonist, had no effect on PND 13 and then increased the ASR on PND 17 and 21. The 5-HT2 receptor antagonists cyproheptadine (5 mg/kg) and ketanserin (5 mg/kg) blocked the effect of MeODMT at both ages, providing some evidence that MeODMT increased the ASR through 5-HT2 receptors. 1-(m-Chlorophenyl) piperazine (mCPP, 1-5 mg/kg), a 5-HT1B agonist, had no effect on ASR amplitude on PND 13 or 17 and then produced a dose-related decrease in the response on PND 21. Generalized depletion of 5-HT by 80-90% in whole-brain and spinal cord, using p-chlorophenylalanine (PCPA, 300 mg/kg 24 hr prior to testing), did not alter ASR amplitude at any age.(ABSTRACT TRUNCATED AT 250 WORDS)
Sheets
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LP
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Cook
L L
LL
Reiter
L W
LW
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000161:Acoustic Stimulation; D000367:Age Factors; D000818:Animals; D000833:Animals, Suckling / Q000502:physiology*; D001923:Brain Chemistry; D003533:Cyproheptadine / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008732:Methoxydimethyltryptamines / Q000494:pharmacology; D009638:Norepinephrine / Q000032:analysis; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000032:analysis / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D008732:Methoxydimethyltryptamines; D010879:Piperazines; D013764:Tetrahydronaphthalenes; D003533:Cyproheptadine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; D010134:Fenclonine; C015068:1-(3-chlorophenyl)piperazine; D004298:Dopamine; D009638:Norepinephrine