Distinct functions for dopamine and serotonin in locomotor behaviour: evidence using the 5-HT1 agonist RU 24969 in globus pallidus-lesioned rats.

The locomotor effect of RU 24969, a potent 5-HT1 agonist, was tested in two experimental conditions. Firstly, 5-HT neurons were degenerated by i.c.v. infusion of 5,7-dihydroxytryptamine (5,7-DHT). Secondly, outputs of the nigrostriatal and mesolimbic dopaminergic (DAergic) systems were bilaterally disrupted by electrolytic lesion of the globus pallidus (GP). After both types of lesion, RU 24969 (1.25-5 mg/kg, i.p.) induced an intense and long-lasting hyperlocomotion which was more pronounced than in intact rats. The hyperlocomotion induced in 5,7-DHT lesioned rats as well as that in intact rats was abolished by the DA blocker haloperidol (0.5 mg/kg, i.p.). On the contrary the hyperlocomotion induced in GP-lesioned rats was either unmodified or increased both by haloperidol even at a very high dose (2 mg/kg, i.p.) and by methysergide (5 mg/kg, i.p.). It is concluded that (i) there is no DAergic link in the locomotor response to RU 24969, (ii) 5-HT1 receptors are involved in the motor execution of locomotion, (iii) DA initiates and controls the 5-HT-mediated locomotion in normal rats.