Effect of 5-HTP and ketanserine on the aggressive reaction induced by food competition in dominant and submissive pigeons (Columba livia).

There is abundant literature about the effects of manipulation of 5-hydroxytryptamine (5-HT) systems on some killer behaviors as well as on social isolation and shock-induced aggression in rodents. In this work we have analyzed the effect of 5-HT manipulation on the aggressive behavior induced by food competition in undernourished pigeons. Adult males (n = 12) were caged individually and their body weight kept at 80-85% by a restricted diet. These were divided in pairs which were exposed daily to an aggressive interaction test (20 min) in a 1.5 x 1.5 x 2.0 m chamber bearing a central feeding device. Once consolidation of dominance was obtained in each pair, the dominant and the submissive members were injected subcutaneously, on alternating days, with 5-hydroxytryptophan (5-HTP) (7.5, 15 and 30 mg/kg), ketanserine (20 and 30 mg/kg) and a combination of ketanserine (20 mg/kg) and 5-HTP (7.5 mg/kg). Aggression was evaluated by scoring the frequency and time spent biting, wing beating, aggressive following and vocalizations, threatening and pushing the opponent in 20-min tests. The time spent running away was also scored. Intratest feeding was ascertained by weighing the subjects immediately before and after testing. The scores were compared with those obtained after saline injection on the preceding day (C-scores). 5-HTP (7.5 mg/kg) attenuated aggression without affecting feeding in dominant members, and decreased the time spent running away by submissives. Higher doses of 5-HTP decreased feeding but did not potentiate the anti-aggressive effects. The 5-HT2 antagonist, ketanserine did not affect aggression but decreased feeding at the dose of 30 mg/kg. Ketanserine injection clearly prevented the anti-aggressive effects of 5-HTP but caused a decrease of feeding. Results show that 5-HT stimulation in pigeons can preferentially block aggression in this particular experimental situation. It is suggested, in addition, that 5-HT2 receptors might be involved in such an effect.

The effect of dantrolene sodium on rat skeletal muscle in relation to the plasma concentration.

Dantrolene sodium is a muscle relaxant used in the treatment of spasticity. It has been shown to interfere with calcium release from the sarcoplasmic reticulum and thus to inhibit excitation--contraction coupling. The effect of dantrolene sodium on the twitch tension of the tibialis anterior muscle of the rat was measured after 2 mg/kg i.v. or 25 mg/kg orally. Plasma concentrations were estimated at maximum twitch depression and during recovery from the block. In a separate series of experiments the half-life of labelled dantrolene sodium was measured in blood plasma, skeletal muscle and heart muscle of rats. Dantrolene sodium 2 mg/kg i.v. gave a maximal block of approximately 47%, the mean dantrolene sodium concentration was then 5.8 microgram/ml. A half-life for distribution of 1.1 min and an elimination half-life of 31 min after intravenous administration were observed, elimination rate constants in skeletal and heart muscle were comparable. Recovery from the block went much slower, the half-time of the process being approximately 80 min. Dantrolene sodium 25 mg/kg orally gave a maximal block of approximately 38% at a mean plasma concentration of 3.6 microgram/ml after 14 min. The recovery was again very slow. These experiments demonstrated that dantrolene sodium acts according to a two-compartment pharmacokinetic model. There was a discrepancy between duration of effect and plasma concentration of dantrolene sodium in the rat. This suggests that the receptor for dantrolene sodium is not located in the central compartment.