Stimulation of serotonin (5-HT)1A receptors attenuates the locomotor, but not the discriminative, effects of amphetamine and cocaine in rats

The influence of serotonin (5-HT)(1A) receptor stimulation on the dopamine (DA)-mediated locomotor and discriminative behaviours was evaluated in rats. The increased locomotor activity induced by the indirect DA agonist amphetamine (0.5 mg/kg) or cocaine (5 mg/kg) was dose-dependently inhibited by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.125-0.5 mg/kg), a 5-HT1A agonist. (S)-N-tert-butyl-3-[4-(2-methoxyphenyl)piperazin-1-yl]-2-phenylpropanamide (WAY 100135; 10 mg/kg), a selective 5-HT1A antagonist, did not change the hyperactivity induced by amphetamine or cocaine, but it reduced the inhibitory effect of 8-OH-DPAT on the hypermotility evoked by either psychostimulant. In drug discrimination experiments, 8-OH-DPAT (0.125-0.5 mg/kg) did not antagonize the stimulus effects of amphetamine (0.5 mg/kg) or cocaine (5 mg/kg). When given in combination with amphetamine (0.025-0.5 mg/kg) or cocaine (0.25-5 mg/kg), 8-OH-DPAT (0.5 mg/kg) did not modify the dose-response curves of those psychostimulants. The obtained results indicate that 8-OH-DPAT inhibits the amphetamine- or cocaine-induced increases in the locomotor activity in rats via stimulation of 5-HT1A receptors. On the other hand, the lack of the antidiscriminative effects of 8-OH-DPAT suggests that the two effects of amphetamine and cocaine are not modified in the same way by 5-HT1A receptors.