Increased levels of 5-HT1A receptor binding in ventral visual pathways in Parkinson's disease

Visual hallucinations are common in advanced Parkinson's disease (PD). The pathophysiology of visual hallucinations may involve enhanced serotonergic neurotransmission. The atypical antipsychotics clozapine and quetiapine, which have affinity for 5-HT2A and 5-HT1A receptors, are effective against visual hallucinations in PD. 5-HT2A receptors are increased in ventral visual pathways in PD patients with visual hallucinations, and we hypothesized that 5-HT1A receptors were also involved in visual hallucinations in PD. Autoradiographic binding using [3H]-WAY-100,635 and NAN-190 was performed in brain sections from 6 PD patients with visual hallucinations, 6 PD patients without visual hallucinations, and 5 age-matched controls. All PD subjects had been treated with L-dopa. Brain areas studied were the orbitofrontal, inferolateral temporal, and motor cortices, as well as the striatum, globus pallidus, substantia nigra, and thalamus. 5-HT1A-binding levels were dramatically increased in the ventral visual pathways of all PD patients compared with controls (0 vs 11 and 0 vs 100 nmol/mg, respectively; both P < .05). There was no significant difference in 5-HT1A-binding levels in PD patients with visual hallucinations compared with PD patients without visual hallucinations or with controls in any of the brain areas studied (P > .05). Gross abnormalities in 5-HT1A levels in ventral visual areas occurred in all PD patients exposed to L-dopa. However, as there was no difference in 5-HT1A-binding levels between hallucinators and nonhallucinators, alterations in 5-HT1A receptor levels may not contribute specifically to visual hallucinations in PD. However, the discrete anatomical distribution of rises to the ventral visual areas suggests some role in predisposing to visual hallucinations. (C) 2012 Movement Disorder Society