Interakcja pomiędzy ośrodkowym układem noradrenergicznym a działaniem przeciwbólowym pośredniczonym przez receptor serotoninergiczny 5-HT3 u szczurów
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Department of Pharmacology, Medical University of Silesia, 41-808 Zabrze, Poland
Przemysław Nowak   

Katedra i Zakład Farmakologii Śląskiego Uniwersytetu Medycznego ul. H. Jordana 38, 41-808 Zabrze tel./fax +48 32 272 26 83
Ann. Acad. Med. Siles. 2010;64:7–17
The aim of the present study was to examine the impact of the central noradrenergic system on the serotoninergic 5-HT3 receptor mediated analgesia in rats.

Material and Methods:
The noradrenergic system was lesioned in male rats shortly after birth by subcutaneous (sc) injections of the neurotoxin DSP-4 [(N-(-2-chloroethyl)- N-ethyl-2-bromobenzylamine (50 mg/kg x 2) given on postnatal days 1 and 3. Rats continued to be housed until they were 10 weeks old, for further experimentation. The anti-nociceptive eff ects of the central serotoninergic 5-HT3 receptor agonist (1-phenylbiguanide; 7.5 mg/kg), antagonist (ondansetron; 1.0 mg/kg) and both drugs administration (intraperitoneal; ip) were examined in models of exteroceptive sensation using thermal (tail immersion and hot plate tests) and mechanical stimuli (paw pressure test). Furthermore accumulation of 5-hydroxytryptamine (5-HTP) in some parts of the brain were determined using high pressure chromatography with electrochemical detection method (HPLC/ED).

Results and Conclusions:
In the tail immersion test we did not observe diff erences between control and DSP-4 treated rats as far as the anti-nociceptive eff ect evoked by the central serotoniergic 5-HT3 receptor agonist (1-phenylbiguanide; 7.5 mg/ kg ip) is concerned. Conversely in the hot plate test 1-phenylbiguanide (7.5 mg/kg ip) produced signifi cantly diminished analgesic reaction in DSP-4 lesioned rats in comparison to control (in all tested intervals (20, 40, 60 and 80 min; p <0.05); this eff ect was abolished by 5-HT3 receptor antagonist (ondansetron; 1.0 mg/kg ip) pretreatment. Similar eff ects were observed in paw pressure test; in this case signifi cant changes were noticed in 20 and 40 min of testing (p <0.05). In biochemical assay we found that 1-phenylbiguanide signifi cantly increased 5-HTP level in the prefrontal cortex of control rats being without eff ect in DSP-4 group in this regard. Ondansetron did not aff ect 5-HTP content when given alone but injected before 1-phenylbiguanide abolished its eff ect in control group. In the thalamus with hypothalamus (control) as well as in the brain stem (control and DSP-4) 1-phenylbiguanide only non-signifi cantly elevated 5-HTP level. Ondansetron alone did not aff ect examined parameters but in the brain stem administered before 1-phenylbiguanide statistically lowered 5-HTP (in both tested groups) in comparison to respective controls (1-phenylbiguanide). The results of the present study indicate that the noradrenergic system participates in the analgesic properties of 5-HT3 acting drugs integrated in the higher brain structures (e.g. thalamus, cortex) being without eff ect on spinal analgesia. Additionally, obtained data pointed out on the possibility of nociception disturbances (mediated by 5-HT3 receptor)

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