Malka Israeli

Autoradiographic analysis of serotonin 5-HT1A receptor binding in the human brain postmortem : effects of age and alcohol

Quantitative autoradiographic analysis of serotonin 5-HT1A receptors in the human brain, using [3H]8-OH-DPAT as a ligand, reveals region-specific decreases in receptor labeling with age in several cortical and hippocampal regions and in the raphe nuclei. This is due to a change in receptor density (Bmax) with no apparent change in affinity (Kd) as affirmed by saturation binding analysis on representative cortical regions. The presence of alcohol is associated with decreased binding in several cortical gyri. Suicide, gender and postmortem delay had no effect on 8-OH-DPAT binding.

Regionally selective increases in β-adrenergic receptor density in the brains of suicide victims

The effect of ageing and suicide on mu opioid receptors was studied in the human brain postmortem. Quantitative autoradiography with [3H]DAGO revealed region specific increases in mu receptor density with age. Suicide was accompanied by a significant increase, up to 9-fold, in mu receptor density in the young, but not the old, subjects as compared to age-matched controls. This effect was evident in the frontal and temporal cortical gyri. Saturation binding studies with the same ligand show that the increased binding in the elderly and in the young suicides is due to an increase in receptor density (Bmax) rather than affinity (Kd).

Autoradiographic analysis of [3H]ketanserin binding in the human brain postmortem: effect of suicide.

In vitro quantitative autoradiography of 5-HT2 receptors, using [3H]ketanserin as a ligand, was performed on 24 human brains postmortem. Twelve brains were donated by suicide victims and 12 by matched controls. We found a characteristic decline in 5-HT2 receptors with age in several brain regions of the control group. This age dependence of ketanserin binding was not present in some of these brain regions of the suicide group. We also found a significant but anatomically selective reduction in the density of ketanserin binding sites in the young suicide group, compared to age-matched controls. This reduction was evident in portions of the prefrontal cortex. Homogenate binding assays on prefrontal cortex samples from a large group of suicides (n = 20) and controls (n = 23) showed that the difference in age dependence of ketanserin binding and the reduced binding in the young suicide group were explained by differences in Bmax values. No differences were observed in Kd. Sex, presence of alcohol and time from death to autopsy did not affect ketanserin binding, in our sample, as measured by either autoradiography or homogenate binding assay.

Autoradiographic analysis of age-dependent changes in serotonin 5-HT2 receptors of the human brain postmortem.

Autoradiographic analysis of 5-HT2 receptors in the human brain, using [3H]ketanserin as a ligand, reveals region-specific changes in receptor labeling as a function of age. In the prefrontal cortex and hippocampal dentate gyrus of 12 normal subjects, label density decreases sharply with age over the 2nd and 3rd decades, reaches a minimum around age 50 and then starts to increase again in the 6th and 7th decades. Other brain regions studied, including frontoparietal and temporal cortex, basal ganglia and thalamus, did not show significant changes with age. Saturation binding experiments on prefrontal cortical samples from 23 normal subjects reveal that the decrease in label density is due to changes in receptor density (Bmax) with no apparent change in affinity (Kd). Sex, presence of alcohol and postmortem delay had no effect on ketanserin binding.

Serotonin 5-HT2 receptor binding on blood platelets as a state dependent marker in major affective disorder

Serotonin receptors of the 5-HT2 type were studied on platelet membranes from 15 patients suffering from major depression. Receptor binding and clinical state (assessed by the Hamilton and Beck rating scales) were examined in a drug free state upon admission and after 1 and 3 weeks of treatment with the antidepressant maprotiline (MPT). 5-HT2 receptor binding changed in correlation with changes in the clinical state of the patients as judged by the rating scales. Since most patients showed a clinical improvement, the patients as a group exhibited a significant decrease in binding concomitant with a drop in depression scores. However, in those patients in whom there was no clinical change or an increase in depression scores, 5-HT2 receptor binding did not change or increased, respectively, thus resulting in a significant correlation between clinical changes and changes in binding. These results support the use of 5-HT2 receptors on platelets in evaluating depression and its treatment.

Autoradiographic analysis of [3H]desmethylimipramine binding in the human brain postmortem

In vitro quantitative autoradiography of high-affinity [3H]desmethylimipramine (DMI) binding sites was performed on 24 human brains postmortem. Highest densities of binding sites were found in portions of the amygdala, the granular layer of the dentate gyrus, the pyramidal layer of CA4. Next, in descending order were other portions of the hippocampus and amygdala, the head of the caudate nucleus, putamen, hypothalamus, insular cortex, prefrontal cortex, parietal, frontal and temporal cortex, anterior, medial and posterolateral nuclei of the thalamus. Lowest densities, hardly above background, were found in the two divisions of the globus pallidus, the centromedian, ventrolateral and posteroventral lateral nuclei of the thalamus, substantia nigra, red nucleus and white matter. Specific high-affinity [3H]DMI binding was not affected by age, sex and suicide in any of the regions studied. It was negatively correlated with postmortem delay in several regions.

Localization of the effects of electroconvulsive shock on β-adrenoceptors in the rat brain

Chronic (10 days) application of electroconvulsive shock (ECS) to male and female rats results in a significant but highly localized decrease in beta-adrenoceptor number. Saturation studies on homogenized tissue revealed a decrease in Bmax in the frontal cortex and hippocampus but not in caudate or cerebellum of both sexes. Quantitative autoradiographic analysis showed the changes in the hippocampus to be in the CA1 and dentate gyrus but not CA3. No effect was seen in caudate, globus pallidus, substantia nigra, cerebellar molecular and granular layers and several thalamic and hypothalamic nuclei.

Quantitative Autoradiographic Analysis of the Effects of Electroconvulsive Shock on Serotonin-2 Receptors in Male and Female Rats

Abstract: Chronic electroconvulsive shock (ECS) is known to increase the level of serotonin‐2 (S2) receptors in male rat brain. Using quantitative autoradiography, we have studied the distribution pattern of these receptors in female as well as male rats and the effect of repeated ECS on the receptor level in both sexes. We find that although the distribution of S2 receptors is generally similar in males and females, they respond differently to repeated ECS. In males we found the expected increase in S2 binding, which was localized to specific cortical, hippocampal, and septal regions. In females, no increase was found in the cortex or septum and relatively small increases were found in the hippocampus. It appears that the regulation of S2 receptors by ECS is sex‐dependent.

Reduction in serotonin 5HT2 receptor binding on platelets of delinquent adolescents

The possible involvement of serotonin receptors of the 5HT2 type in aggressive behavior was studied in juvenile delinquents. A group of 28 delinquent adolescents (13–18 years old) who had committed violent crimes was compared with a group of age matched controls. Subjects were drug and medication free during the study. 5HT2 receptors were labeled on platelet membranes using tritiated ketanserin. Receptor binding in the delinquent adolescents was significantly lower than in age matched controls. Mean ± SD of 76 controls was 32.3±14.2 fm/mg, compared to 16.6±8.2 fm/mg in 28 delinquents (P<0.002, Studentst-test). These results support a role for serotonin in general and 5HT2 receptors in particular in human aggressive behavior.

Unaltered α2-noradrenergic/imidazoline receptors in suicide victims: a postmortem brain autoradiographic analysis

In vitro quantitative autoradiography of alpha(2)-adrenergic/imidazoline receptors, using [(125)I]iodoclonidine as a ligand, was performed on 24 human brains postmortem. Twelve brains were obtained from suicide victims and 12 from matched controls. We found no significant, region-dependent alterations in the density of alpha(2)-adrenergic receptors in brains of suicide victims as compared to matched controls. We also report age-dependent reductions in binding in the prefrontal cortex and hippocampus, as well as significant recent alcohol ingestion-dependent reductions in binding in the prefrontal cortex. Sex and time from death to autopsy did not affect iodoclonidine binding in our sample.