J. thvrm. B.d. V~d. II. No. I. pp. 53 57. 1986 0306-4565,86 $3.0(1.4 ().(Ill Prinled in Great Brilam Pcrg:ttllon Jt~urnal.: I.Id ALTERATION OF 5-HYDROXYTRYPTOPHAN-INDUCED HYPOTHERMIA BY SEROTONERGIC AGENTS IN THE ADULT DOMESTIC FOWL (GALLUS DOMESTICUS) GAIIRII-L OSUII)I'. CIIARLI:~S WAMIn'Bt'* and SUBHASli BOI)HANKAR Department of Pharmacology, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria, Nigeria (Receh,ed 17 Apri/ 1985; accepted br revised fi~rm II November 1985) Al~tract--I. 5-Hydroxytryptophan (5-HTP) induced a dose.dependent hypothermia in adult fowls. 2. The hypothermic effect of 5-HTP was potentiated by carbidopa, citalopram, additive with ( + ), ( - ) and (+) propranolol and antagonised by methysergide and metitepine. 3. Cyproheptadine, xylamidine and ketanserin did not antagonise 5-HTP-induced hypothermia. 4. The results suggest that the hypothermic effect of 5-HTP in fowls may be mediated mainly via activation of central 5-HT receptors, probably 5-HTI receptors. Key Word lndex--5-HTP; serotonergic agents; rectal temperature; adult fowls. INTRODUCTION It has been reported that 5-hydroxytryptophan (5-HTP) induces a profound hypothermia in young chicks (Osuide et aL, 1984). Here, the effect of 5-HTP on rectal temperature of adult fowls has been investi- gated with special reference to the possible peripheral or central components of the response. Various specific peripheral and central 5-HT receptor antag- onists were used to compare the receptor blocking profiles of these drugs and possible involvement of specific 5-HT receptors. MATERIALS AND METHODS Adult cocks, 4--6 months old and weighing I-I.5 kg were obtained locally. They were allowed 1 h to acclimatize to the laboratory conditions before commencing any temperature measurement and had access to food and water. The rectal temperature w~,s recorded with the aid of an Edale thermistor thermometer, model K (Edale Instruments, Cambridge, England). The thermistor probes were inserted into the bird's rectum to a distance of about 3 cm to give reproducible measure- ments. The experiments were performed in a quiet, air-conditioned room at an ambient temperature of 24 __+ 2'C. The experiments were performed between 09.00 and 14.00 h daily to keep uniform circadian oscillations of temperature. The experiments ~vere performed using 4 fowls per dose of the drug. The temperature recordings were done at 10 rain intervals for I It before and up to 3 h after drug administration. The drug solutions were freshly prepared in ph 3sio- logical saline (0.9% NaCI) or an appropriate solvent belorc intraperitoncal injection. All drug concen- trations refer to the salts, except those of para- chlorophcnylalaninc (PCPA) methyl ester which rcl'cr *To whom all correspondence should bc addressed to its base (125.33 g of it was equivalent to 100 g of para--chlorophenylalanine base). Control chicks were injected with 0.4 mi of physiological saline. Carbi- dopa was suspended in 30/, tween 80 after which the suspension was diluted with physiological saline prior to an intraperitoneal injection. Ketanserin was dis- solved in 0. I M tartaric acid, 5-HTP was dissolved in physiological saline and stabilized by the addition of 0. 1% w/w sodium metabisulphite. 5-HTP and PCPA were purchased from Sigma Chemical Company, UK. The pretreatment time for citaiopram, methyser- gide and metitepine was 30 rain, carbidopa, cypro- heptadine, mianserine, ketanserin was 1 h while that of xylamidine was 4h (Beaton and Kuhlemeier, 1980). Fowls were pretreated with PCPA (300 mg/kg i.p.); this amount was divided into three doses of 100 mg/kg per day before temperature measurement or 5-HTP injection. The timings were in accordance with earlier work (Osuide et al., 1984). It was observed that 5-HTP-induced hypothermia was maximal at 100rain post-injection. Thus, the results obtained at 100 min after 5-HTP administra- tion were used for statistical analysis using Student's t-test. A P level of 0.05 was regarded as significant statistically. RESULTS Eff~,ct o/physiological saline Physiological saline produced a slight but insignilicant hypothermia (0.2+ 12 C). The rectal temperature of the fowls was 41.8 +_0.14C. EJ]~'ct ~,[ 5-11TP alone A dose of 8 mg 5-HTP/kg had no effect on the rectal temperature but at higher doses ( 16-64 mg/kg) a dose-dependent hypothermia developed (Table I). The mean of the onset and duration of hypothcrmm were respectively, 201nin and 12(Imin after 5-flTP 53