R(+)-8-OH-DPAT, a serotonin(1A) receptor agonist, potentiated S(-)-sulpiride-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens but not striatum.
The serotonin (5-HT)(2A/2C) receptor antagonist ritanserin has been reported to potentiate the dopamine (DA) D(2/3) receptor antagonist raclopride-induced DA release in medial prefrontal cortex (mPFC) and nucleus accumbens (NAC) but not striatum (STR). Because of reciprocal interactions between 5-HT(2A) and 5-HT(1A) receptors, we tested the hypothesis that 5-HT(1A) receptor agonism also potentiates D(2/3) receptor antagonist-induced DA release using a combination of the 5-HT(1A) receptor agonist R(+)-8-hydroxy-2-(di-n-propylamino)-tetralin [R(+)-8-OH-DPAT] and the D(2/3) receptor antagonist S(-)-sulpiride (SUL). R(+)-8-OH-DPAT (0.05 mg/kg s.c.) potentiated low but not high dose SUL (1, 3 but not 10 or 25 mg/kg s.c.)-induced DA release in NAC, but had no effect in STR at all doses tested (1, 3, 10, and 25 mg/kg s.c.). However, R(+)-8-OH-DPAT (0.05 mg/kg s.c.) alone had no effect on basal, potentiated SUL (10 and 25 mg/kg s.c.)-induced DA release in mPFC; the effect of low dose SUL (1 and 3 mg/kg s.c.) was not tested because it alone had no effect on DA release. This potentiation was abolished by pretreatment with the 5-HT(1A) receptor antagonist WAY100635 (0.05 mg/kg s.c.), which alone had no effect on DA release. These results suggest that 5-HT(1A) receptor agonism facilitates DA release in mPFC and NAC but not STR in combination with D(2) receptor antagonism.
Ichikawa
J
J
Department of Psychiatry, Psychopharmacology Division, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. ichikaj@ctrvax.vanderbilt.edu
Meltzer
H Y
HY
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004357:Drug Synergism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013469:Sulpiride / Q000494:pharmacology*
D018492:Dopamine Antagonists; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D013469:Sulpiride; D004298:Dopamine