The effect of serotonergic agents on haloperidol-induced striatal dopamine release in vivo: opposite role of 5-HT2A and 5-HT2C receptor subtypes and significance of the haloperidol dose used
Neuropharmacology. 2000-05-01; 39(6): 1053-1063
DOI: 10.1016/S0028-3908(99)00193-8
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This study investigated, using microdialysis in freely-moving rats, the role of
serotonin (5-HT) and 5-HT(2) receptor subtypes in the enhancement of striatal
dopamine (DA) release induced by various doses of haloperidol. The subcutaneous
injection of 0.01, 0.1 or 1 mg/kg haloperidol dose-dependently increased DA
outflow (160, 219 and 230% of baseline, respectively). The effect of 0.01 mg/kg
haloperidol was, respectively, potentiated by the 5-HT uptake inhibitor
citalopram (1 mg/kg, s.c.; +35%) and reduced by the 5-HT(1A) receptor agonist
8-OH-DPAT (0.025 mg/kg, s.c.; -32%). Also, it was reduced by the 5-HT(2A)
antagonist SR 46349B (0.5 mg/kg, s.c. ; -40%) or by the 5-HT(2A/2B/2C)
antagonist ritanserin (1.25 mg/kg, i.p.; -34%), and potentiated by the
5-HT(2B/2C) antagonist SB 206553 (5 mg/kg, i.p; +78%). Further, only this latter
compound significantly modified basal dopamine release by itself (+26%).
Dopamine released by 0.1 mg/kg haloperidol was enhanced (+100%) by citalopram,
decreased (-61%) by SR 4634B, but unaltered by SB 206553. Finally, none of the
compounds used were able to modify the enhancement of dopamine release induced
by 1 mg/kg haloperidol. These results show that central 5-HT(2A) and 5-HT(2C)
receptors exert an opposite (respectively excitatory and inhibitory) influence
on DA release. Moreover, they suggest that the 5-HT(2A)-dependent modulation
depends on the degree of central DA receptor blockade.
DOI: 10.1016/s0028-3908(99)00193-8
PMID: 10727716 [Indexed for MEDLINE]