Novelty-seeking personality traits are a major risk factor for the development of drug abuse and other unsafe behaviors. Rodent models of temperament indicate that high novelty responding is associated with decreased inhibitory autoreceptor control of midbrain dopamine neurons. It has been speculated that individual differences in dopamine functioning also underlie the personality trait of novelty seeking in humans. However, differences in the dopamine system of rodents and humans, as well as the methods for assessing novelty responding/seeking across species leave unclear to what extent the animal models inform our understanding of human personality. In the present study we examined the correlation between novelty-seeking traits in humans and

This study examined D-amphetamine (D-AMPH)-induced displacements of [18 F] fallypride in striatal and extrastriatal regions and the correlations of these displacements with cognition, affect, and sensation-seeking behavior. In all, 14 normal subjects, six females and eight males (ages 21-32, mean age 25.9 years), underwent positron emission tomography (PET) with [18 F]fallypride before and 3 h after a 0.43 mg/kg oral dose of D-AMPH. Levels of dopamine (DA) D 2 receptor density were calculated with the reference region method of Lammerstma. Percent displacements in striatal and extrastriatal regions were calculated for the caudate, putamen, ventral striatum, medial thalamus, amygdala, substantia nigra, and temporal cortex. Correlations of changes in cognition, affect, and sensation seeking with parametric images of D-AMPH-induced DA release were computed. Significant displacements were seen in the caudate, putamen, ventral striatum substantia nigra, and temporal cortex with a trend level change in the amygdala. Greatest displacements were seen in striatal subdivisionsF5.6% in caudate, 11.2% in putamen, 7.2% in ventral striatum, and 6.6% in substantia nigra. Lesser decrements were seen in amygdalaF4.4%, temporal cortexF3.7%, and thalamusF2.8%. Significant clusters of correlations of regional DA release with cognition and sensation-seeking behavior were observed. The current study demonstrates that [ 18 F]fallypride PET studies using oral D-AMPH (0.43 mg/kg) can be used to study D-AMPH-induced DA release in the striatal and extrastriatal regions in humans, and their relationship with cognition and sensation-seeking behavior.

Clozapine and quetiapine have a low incidence of extrapyramidal side effects at clinically effective doses, which appears to be related to their significantly lower occupancy of striatal dopamine D 2 receptors (DA D 2 r) compared to typical antipsychotic drugs (APDs). Animal studies have indicated that clozapine and quetiapine produce selective effects on cortical and limbic regions of the brain and in particular on dopaminergic neurotransmission in these regions. Previous PET and SPECT studies have reported conflicting results regarding whether clozapine produces preferential occupancy of cortical DA D 2 r. To examine whether clozapine and/or quetiapine produce preferential occupancy of DA D 2 r in cortex and limbic regions, we studied the occupancy of putamenal, ventral striatal, thalamic, amygdala, substantia nigra, and temporal cortical DA D 2 r using PET with [18 F]fallypride in six schizophrenic subjects receiving clozapine monotherapy and in seven schizophrenic subjects receiving quetiapine monotherapy. Doses were chosen clinically to minimize psychopathology at tolerable levels of side effects such as drowsiness. All had minimal positive symptoms at the time of the study. Regional receptor occupancies were estimated using mean regional DA D 2 r levels calculated for 10 off-medication schizophrenic subjects. Both clozapine and quetiapine produced lower levels of putamenal DA D 2 r occupancy than those reported for typical APDs, 47.8 and 33.5%, respectively. Clozapine produced preferential occupancy of temporal cortical vs putamenal DA D 2 r, 59.8% (p ¼ 0.05, corrected for multiple comparisons), and significantly lower levels of occupancy in the substantia nigra, 18.4% (p ¼ 0.0015, corrected for multiple comparisons). Quetiapine also produced preferential occupancy of temporal cortical DA D 2 r, 46.9% (p ¼ 0.03, corrected for multiple comparisons), but did not spare occupancy of substantia nigra DA D 2 r. The therapeutic effects of clozapine and quetiapine appear to be achieved at less than the 65% threshold for occupancy seen with typical APDs, consistent with the involvement of non-DA D 2 r mechanisms in at least partially mediating the therapeutic effects of these drugs. Preferential occupancy of cortical DA D 2 r, sparing occupancy of substantia nigra receptors, and non-DA D 2 r-mediated actions may contribute to the antipsychotic actions of these and other atypical APDs.

Background-Studies in schizophrenics have reported dopaminergic abnormalities in striatum, substantia nigra, thalamus, anterior cingulate, hippocampus and cortex which have been related to positive symptoms and cognitive impairments.

Findings revealed a greater dopamine release in women as well as gender differences in the relationship between regional dopamine release and sensation seeking and cognition.

In the early phase of AMI, serum IGF-1 levels are markedly reduced and may contribute to adverse outcomes. Reduced IGF-1 preceding the rise of myocardial necrosis markers suggests a possible pathogenetic role. A compensatory increase in IGF-1 appears to occur by one year.

There have been conflicting reports as to whether olanzapine produces lower occupancy of striatal dopamine D 2 /D 3 receptor than typical antipsychotic drugs and preferential occupancy of extrastriatal dopamine D 2 /D 3 receptors. We performed [18 F] fallypride PET studies in six schizophrenic subjects treated with olanzapine and six schizophrenic subjects treated with haloperidol to examine the occupancy of striatal and extrastriatal dopamine receptors by these antipsychotic drugs. [18 F] setoperone PET studies were performed in seven olanzapine-treated subjects to determine 5-HT 2A receptor occupancy. Occupancy of dopamine D 2 /D 3 receptors by olanzapine was not significantly different from that seen with haloperidol in the putamen, ventral striatum, medial thalamus, amygdala, or temporal cortex, that is, 67.5-78.2% occupancy; olanzapine produced no preferential occupancy of dopamine D 2 /D 3 receptors in the ventral striatum, medial thalamus, amygdala, or temporal cortex. There was, however, significantly lower occupancy of substantia nigra/VTA dopamine D 2 /D 3 receptors in olanzapine-treated compared to haloperidol-treated subjects, that is, 40.2 vs 59.3% (p ¼ 0.0014, corrected for multiple comparisons); in olanzapine-treated subjects, the substantia nigra/VTA was the only region with significantly lower dopamine D 2 /D 3 receptor occupancy than the putamen, that is, 40.2 vs 69.2% (po0.001, corrected for multiple comparison). Occupancy of 5-HT 2A receptors was 85-93% in the olanzapine-treated subjects. The results of this study demonstrated that olanzapine does not produce preferential occupancy of extrastriatal dopamine D 2 /D 3 receptors but does spare substantia nigra/VTA receptors. Sparing of substantia nigra/VTA dopamine D 2 /D 3 receptor occupancy may contribute to the low incidence of extrapyramidal side effects in olanzapine-treated patients.

The relationship between cerebral morphology and the expression of dopamine receptors has not been extensively studied in humans. Elucidation of such relationships may have important methodological implications for clinical studies of dopamine receptor ligand binding differences between control and patient groups. The association between cerebral morphology and dopamine receptor distribution was examined in 45 healthy subjects who completed T1-weighted structural MRI and PET scanning with the D 2 /D 3 ligand [ 18 F]fallypride. Optimized voxel-based morphometry was used to create grey matter volume and density images. Grey matter volume and density images were correlated with binding potential (BP ND ) images on a voxel-by-voxel basis using the Biological Parametric Mapping toolbox. Associations between cerebral morphology and BP ND were also examined for selected regions-of-interest (ROIs) after spatial normalization. Voxel-wise analyses indicated that grey matter volume and density positively correlated with BP ND throughout the midbrain, including the substantia nigra. Positive correlations were observed in medial cortical areas, including anterior cingulate and medial prefrontal cortex, and circumscribed regions of the temporal, frontal, and parietal lobes. ROI analyses revealed significant positive correlations between BP ND and cerebral morphology in the caudate, thalamus, and amygdala. Few negative correlations between morphology and BP ND were observed. Overall, grey matter density appeared more strongly correlated with BP ND than grey matter volume. Cerebral morphology, particularly grey matter density, correlates with [ 18 F]fallypride BP ND in a regionally specific manner. Clinical studies comparing dopamine receptor availability between clinical and control groups may benefit by accounting for potential differences in cerebral morphology that exist even after spatial normalization.