5-HT1A autoreceptor stimulation can act to attenuate supraphysiological swings 
in extracellular dopamine levels following long-term levodopa treatment and may 
be useful in the treatment and prevention of the motor complications. The 
purpose of this study was to investigate cellular and behavioral effects of 
5-HT1A receptor agonist 8-OH-DPAT in a rat model of levodopa-induced motor 
complications. Two sets of experiments were performed. First, animals were 
treated with levodopa (50 mg/kg with benserazide 12.5 mg/kg, twice daily), 
intraperitoneally (i.p.) for 22 days. On day 23, animals received either 
8-OH-DPAT (1 mg/kg, i.p.) or 8-OH-DPAT plus WAY-100635 (0.1 mg/kg, i.p) or 
vehicle with each levodopa dose. In the second set, animals were treated either 
with levodopa (50 mg/kg, i.p.) plus 8-OH-DPAT (1 mg/kg, i.p.) or levodopa (50 
mg/kg, i.p.) plus vehicle, administered twice daily for 22 consecutive days. Our 
study showed that 8-OH-DPAT plus levodopa both prolonged the duration of the 
motor response and reduced peak turning. 8-OH-DPAT plus levodopa also decreased 
the frequency of failures to levodopa. Co-administration of WAY-100635, a 5-HT1A 
receptor antagonist, with 8-OH-DPAT eliminated the effect of 8-OH-DPAT on motor 
complications indicating that the observed 8-OH-DPAT responses were probably 
mediated at the 5-HT1A autoreceptor. Moreover, 8-OH-DPAT plus levodopa 
significantly reduced hyperphosphorylation of GluR1 at serine 845, which was 
closely associated with levodopa-induced motor complications.