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-HT(2A) and 5-HT(1A) receptors, are effective against visual hallucinations in PD. 5-HT(2A) receptors are increased in ventral visual pathways in PD patients with visual hallucinations, and we hypothesized that 5-HT(1A) receptors were also involved in visual hallucinations in PD. Autoradiographic binding using [(3) H]-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-HT(1A) -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-HT(1A) -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-HT(1A) levels in ventral visual areas occurred in all PD patients exposed to L-dopa. However, as there was no difference in 5-HT(1A) -binding levels between hallucinators and nonhallucinators, alterations in 5-HT(1A) 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.

Increased 5-HT2A receptors in the temporal cortex of parkinsonian patients with visual hallucinations.

Well-formed visual hallucinations (VH) are common in patients with Parkinson's disease (PD). The pathophysiology of VH in PD is unknown but may involve structures mediating visual processing such as the inferior temporal cortex. Serotonergic type 2A (5-HT(2A)) receptors have been linked to many psychiatric disorders, including psychosis. We hypothesized that enhanced 5-HT(2A) receptor levels may be involved in VH in PD. Autoradiographic binding using [(3)H]-ketanserin and spiperone, to define 5-HT(2A) receptors, was performed in 6 PD patients with VH, 6 PD patients without VH, and 5 healthy, age-matched controls. The cerebral regions studied included the orbitofrontal cortex, inferolateral temporal cortex, motor cortex, striatum, and substantia nigra. There was a significant (45.6%) increase in the levels of [(3)H]-ketanserin binding in the inferolateral temporal cortex of PD patients with VH when compared with PD patients without VH (54.3 +/- 5.2 fmol/mg vs. 37.3 +/- 4.3 fmol/mg, P = 0.039). Additionally, there was a significant increase in the levels of 5-HT(2A) receptors in the motor cortex of all PD patients taken as a group when compared with controls (57.8 +/- 5.7 fmol/mg vs. 41.2 +/- 2.6 fmol/mg, P = 0.0297). These results suggest that enhanced 5-HT(2A)-mediated neurotransmission in the inferolateral temporal cortex, a critical structure in visual processing, might be associated with the development of VH in PD. Our results provide new insights into the pathophysiology of VH in PD and provide an anatomical basis to explain why compounds with 5-HT(2A) antagonist activity are effective at alleviating this debilitating complication.