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
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.