Long-term sequential determination of behavioral ontogeny of 5-HT1A and 5-HT2 receptor functions in the rat

Citation
Na. Darmani et B. Ahmad, Long-term sequential determination of behavioral ontogeny of 5-HT1A and 5-HT2 receptor functions in the rat, J PHARM EXP, 288(1), 1999, pp. 247-253
Citations number
27
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
ISSN journal
00223565 → ACNP
Volume
288
Issue
1
Year of publication
1999
Pages
247 - 253
Database
ISI
SICI code
0022-3565(199901)288:1<247:LSDOBO>2.0.ZU;2-C
Abstract
Activation of 5-hydroxytryptamine(1A) (5-HT1A) receptors in rats produces h ypothermia and a number of behaviors [hindleg abduction (HLA), lateral head -weaving (LHW), forepaw treading (FPT), flat body posture (FBP), rollover ( RO), tremor (T), and straub tail (ST)] known collectively as the serotonin syndrome (SS). Stimulation of 5-HT2A receptors produces wet-dog shakes (WDS ), whereas 5-HT2C sites induce back muscle contraction (BMC). We investigat ed the functional ontogeny of the cited receptors in rat pups on postnatal days (PD) 7, 14, 18, 22, 28, 35, 60, and 120 by using (1) the 5-HT1A agonis t 8-hydroxy-2-dipropylaminotetralin (0, 1.25, and 5 mg/kg) to induce the SS and hypothermia and (2) the 5-HT2A/C agonist (+/-)-1-(2,5-dimethoxy-4-iodo phenyl)-2-aminopropane (0, 0.5, and 4 mg/kg) to produce both WDS and BMC. T he age of onset for most symptoms of SS [FBP, HLA, RO, and T] was the first week of life. They attained maximal intensities at ages 7 to 14 days, afte r which their maxima either reduced or dissipated to zero. Per contra, the onset of LHW and FPT required 14 to 18 days, and their maxima developed lat er. The onset of (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-induce d WDS occurred after PD 14, and by PD 18, it reached its maximal intensity, which persisted up to PD 60, after which it declined. The onset of BMC was evident on PD 28 and attained its maximal frequency at ages 90 to 120 days . The results show that different components of SS appear within 14 days of birth, but they mature differentially, whereas the hypothermic effect of 5 -HT1A receptors remains relatively constant during aging. The times of onse t and maturation of WDS were intermediate (between the second and third wee ks of life), whereas BMC required 1 to 2 months for its appearance and matu ration.