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-phenylpro panamide (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.
Przegaliñski
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Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Filip
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013268:Stimulation, Chemical
D018765:Dopamine Uptake Inhibitors; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000661:Amphetamine; D003042:Cocaine