R(+)-8-OH-DPAT, a 5-HT_1A receptor agonist, inhibits amphetamine-induced dopamine release in rat striatum and nucleus accumbens

Systemic administration of R(+)-8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), a selective serotonin (5-hydroxytryptamine, 5-HT)_1A receptor agonist (25, 50, and 100 μg/kg s.c.), administered 30 min prior to d-amphetamine, significantly inhibited the d-amphetamine sulfate (1.0 mg/kg s.c.)-induced increase in extracellular dopamine levels in the striatum and nucleus accumbens of freely moving rats, as determined by in vivo microdialysis. The ability of R(+)-8-OH-DPAT (50 μg/kg s.c.) to inhibit d-amphetamine sulfate (1.0 mg/kg s.c.)-induced increase in extracellular dopamine levels was abolished by WAY 100,635 (n-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-n-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride), a selective 5-HT_1A receptor antagonist (100 μg/kg s.c.), administered 5 min prior to R(+)-8-OH-DPAT in both regions. These results indicate that the 5-HT_1A receptor may exert an inhibitory effect on amphetamine-induced dopamine release.