Abstract
Activation of 5-hydroxytryptamine1A (5-HT1A) receptors in rats produces hypothermia 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 investigated 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 agonist 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-iodophenyl)-2-aminopropane (0, 0.5, and 4 mg/kg) to produce both WDS and BMC. The 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, after 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 later. The onset of (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-induced 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 onset and maturation of WDS were intermediate (between the second and third weeks of life), whereas BMC required 1 to 2 months for its appearance and maturation.
Footnotes
-
Send reprint requests to: Dr. Nissar A. Darmani, Department of Pharmacology, Kirksville College of Osteopathic Medicine, 800 W. Jefferson St., Kirksville, MO 63501. E-mail:Nissard{at}fileserver5.kcom.edu.
-
1 This work was supported by National Institute on Drug Abuse (NIDA) Grant DA07627 and by NIDA-INVEST Grant NO1-DA30002.
- Abbreviations:
- 5-HT
- 5-hydroxytryptamine
- 8-OH-DPAT
- 8-hydroxy-2-dipropylaminotetralin
- PD
- postnatal day
- LHW
- lateral head-weaving
- FPT
- forepaw treading
- FBP
- flat body posture
- ANOVA
- analysis of variance
- DOI
- (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
- HLA
- hindleg abduction
- T
- tremor
- ST
- straub tail
- RO
- rollover
- SS
- serotonin syndrome
- WDS
- wet-dog shakes
- BMC
- back muscle contraction
- CBT
- core body temperature
- HTR
- head-twitch response
- 5-HTP
- 5-hydroxytryptophan
- Received April 15, 1998.
- Accepted August 21, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|