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Saturation binding of [3H]paroxetine was performed in 10 brain regions from a group of suicide victims who had a firm, retrospective diagnosis of depression and who had been prescribed antidepressant drugs, as well as in a group of controls. The number of binding sites did not differ significantly between suicide victims and controls, apart from in putamen, where a lower number of sites was found in the suicide victims. Higher dissociation constant (Kd) values were found in suicide victims dying by antidepressant overdose and also in those dying by other means when compared with controls.

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alpha1-Adrenoceptors and alpha2-adrenoceptors were measured by radioligand binding to homogenates of brain samples obtained at post-mortem from suicides with a retrospective diagnosis of depression, and age and gender-matched controls. Suicides were subdivided into those who had been free of antidepressant drugs for at least three months, and those in whom prescription of antidepressant drugs was clearly documented. The number of alpha1-adrenoceptors (or alpha1A + alpha1D-adrenoceptors) did not differ significantly between antidepressant-free or antidepressant-treated suicides and controls. In antidepressant-free suicides, the number of alpha2-adrenoceptors was significantly higher in temporal cortex (Ba 21/22). alpha2A-Adrenoceptors did not differ significantly from controls in this brain region, suggesting the involvement of other alpha2-adrenoceptor subtypes. In antidepressant-treated suicides, significantly lower numbers of alpha2-adrenoceptors were found in occipital cortex and hippocampus (and for alpha2A-adrenoceptors in caudate and amygdala) compared to controls.

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5-HT1A receptor binding sites were measured, by saturation binding with [3H]8-OH-DPAT, in frontal and occipital cortex, hippocampus and amygdala obtained at post-mortem examination from suicide victims with a firm retrospective diagnosis of depression, and matched controls. The number of 5-HT1A binding sites did not differ significantly between suicides and controls, either in the total sample or when the suicides were divided on the basis of violence of death or recent antidepressant treatment.

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We have measured beta-adrenoceptor binding in pineal glands obtained at post mortem from suicides with a firm retrospective diagnosis of depression, and from age and gender-matched controls. In both antidepressant-free and antidepressant-treated suicides there were no significant differences in the number or affinity of beta-adrenoceptors compared to controls. Within the total group of subjects we found no variation in beta-adrenoceptor binding in relation to time of death or season of death. There was a significant negative correlation between the number of beta-adrenoceptors and age in controls, but not in suicides. These results suggest that pineal beta-adrenoceptors are not altered either in depression or as a result of antidepressant treatment.

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5-HT2 binding sites were quantitated, by saturation binding with [3H]ketanserin, in six brain regions from 73 subjects who died by suicide and 70 sudden death controls. There were no significant differences in the number of 5-HT2 binding sites between suicides and controls in any brain region within the total suicide group or when suicides were divided on the basis of violence of death. Similar results were found when suicides were divided into those with a firm retrospective diagnosis of depression, whether they had been receiving antidepressants or not, and those who were heterogeneous in respect of psychiatric diagnosis and drug treatment. The present findings contrast with previous reports of higher cortical 5-HT2 binding sites in suicides; possible reasons for these differences are discussed.

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In human brain, [3H]glibenclamide binds with high affinity (KD about 3.5 nM) to sulfonylurea binding sites which are associated with ATP-sensitive potassium (KATP) channels. Regarding to the important neuromodulatory action of KATP channels in some neuronal populations, sulfonylurea binding sites were measured in several cortical areas (frontal and temporal cortex, hippocampus) and striatum (caudate nucleus and putamen) in controls and patients with Parkinson's disease or progressive supranuclear palsy. There was no modification of [3H]glibenclamide specific binding in the cerebral regions studied in both pathologies. These results indicate that KATP channels do not seem to be involved in the pathophysiology of these degenerative processes. Brain samples from five patients with Huntington's disease were studied. A small decrease in sulfonylurea binding sites was measured in the frontal cortex, caudate nucleus and putamen which could be due to the loss of either neurons or nerve endings. This low decrease contrasts with the dramatic diminution of many other markers associated with the profound striatal degeneration occurring in Huntington's disease.

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Glutamate receptors of the NMDA-subtype were quantitated by binding of [3H]dizocilpine maleate (MK-801) in nine brain regions from 22 suicide victims (20-60 yr), with a firm retrospective diagnosis of depression, who had not recently received antidepressant drugs, and 20 age- and sex-matched controls. [3H]MK-801-binding did not differ between suicides and controls in any region studied. Suicides who died violently did not differ from non-violent suicides and controls. A significative negative correlation was found between age and NMDA receptor-binding in the frontal cortex of suicide victims, but not in controls. This preliminary study provides little evidence for an important role of NMDA-binding sites in the pathophysiology of depression.

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Total 5-HT1, 5-HT1D and 5-HT1E binding sites were measured in homogenates of human frontal cortex, hippocampus, amygdala, globus pallidus, caudate and putamen. Combined 5-HT1D/1E sites were the predominant 5-HT1 subtype (66-95% of total 5-HT1 sites in all regions except hippocampus (38% of total 5-HT1 sites). Globus pallidus contained the highest density and the highest proportion of 5HT1D sites (74% of total 5-HT1 sites). 5HT1D sites in the other brain areas accounted for 19-27% of the total 5-HT1 sites. The highest densities and the highest proportions of 5-HT1E sites were in caudate (72%) and putamen (64%) and the lowest density and lowest proportion in hippocampus (16%).

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beta-Adrenoceptors were measured by saturation binding of [3H]CGP 12177 in nine brain regions and pineal from suicides, with a firm retrospective diagnosis of depression, and age and sex matched controls. Twenty one suicides had not recently received antidepressant drugs, 17 had been receiving drugs prior to death. In antidepressant drug-free suicides, the number of total beta-adrenoceptors was significant lower in temporal cortex (Brodmann area 38) and beta 1-adrenoceptors (Brodmann areas 21/22) was significant lower than matched controls. Suicides who died by violent means had significantly lower numbers of total beta- and beta 1-adrenoceptors in the frontal cortex and lower numbers of beta 1-adrenoceptors in temporal cortex (Brodmann areas 21/22) than matched controls. Suicides who died by non-violent means had lower numbers of total beta-adrenoceptors in occipital cortex controls and lower numbers of total beta- and beta 1-adrenoceptors in temporal cortex (Brodmann area 38) than matched controls. In antidepressant drug-treated suicides, significantly lower number of beta-adrenoceptor binding sites were found in temporal cortex (Brodmann area 38) and thalamus compared to matched controls. The lower number of beta-adrenoceptors binding sites in the thalamus appeared to be related to drug treatment. There were no differences in beta-adrenoceptor binding in the pineal gland between antidepressant-free and antidepressant-treated suicides and controls, although there were apparent differences between suicides and controls related to the time of death and season of death.

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beta-Adrenoceptor binding sites were measured by saturation binding of [3H]CGP 12177 in nine brain regions from 13 suicides, with a firm retrospective diagnosis of depression, who had been receiving antidepressant drugs, and 11 matched controls. Significantly lower numbers of beta-adrenoceptor binding sites were found in thalamus and temporal cortex (Brodmann area 38), but not in other brain regions, of antidepressant-treated suicides compared to controls. The lower number of beta-adrenoceptor binding sites in thalamus appeared to be related to drug treatment, whereas lower numbers of beta-adrenoceptors in temporal cortex were also found in antidepressant-free suicides.

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Brain serotonin (5-HT) uptake sites were quantitated, by saturation binding of [3H]paroxetine, in 10 brain regions from 22 suicide victims and 20 control subjects. Suicide victims were restricted to those subjects in whom a firm retrospective diagnosis of depression was established and who had not recently been prescribed antidepressant drugs. The Kd and Bmax of [3H]paroxetine did not differ significantly between controls and depressed suicides in any of the brain regions. In putamen, Bmax values of suicides who died non-violently were lower than controls, whereas those who died by violent methods did not differ from controls. No significant differences between violent or non-violent suicides and their matched controls were found in other brain areas. These results offer little support for the view that suicide/depression is associated with an abnormality in 5-HT uptake.

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beta-Adrenoceptor binding sites were quantitated by saturation binding of [3H]CGP 12177 in 9 brain regions from 21 suicide victims, with a firm retrospective diagnosis of depression, who had not recently received antidepressant drugs, and 20 age- and sex-matched controls. In depressed suicides the number of total beta-adrenoceptors was significantly lower in temporal cortex (Brodmann area 38, by 19%) and beta 1-adrenoceptors (Brodmann area 21/22, by 17%) compared to controls. Suicides who died by violent means had significantly lower numbers of total beta- and beta 1-adrenoceptors in frontal cortex than matched controls (by 23 and 25%, respectively) and than non-violent suicides (by 20 and 22%, respectively) and lower numbers of beta 1-adrenoceptors in temporal cortex (Brodmann area 21/22) than matched controls (by 16%). Depressed suicides who died by non-violent means had lower numbers of total beta-adrenoceptors in occipital cortex than matched controls (by 24%) and than violent suicides (by 18%), and lower numbers of total beta- and beta 1-adrenoceptors in temporal cortex (Brodmann area 38) than matched controls (by 27 and 24%, respectively). Depression in suicide victims is associated with deficits in beta-adrenoceptor binding sites, largely restricted to cortical areas.

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beta-Adrenoceptor binding sites were characterised and quantitated in post-mortem human brain with [3H]dihydroalprenolol ([3H]DHA) and [3H]CGP 12177. In cerebral cortex, isoprenaline and propranolol displaced both radioligands with uniform affinity. Practolol and CGP 20712A (selective beta 1-adrenoceptor antagonists) displaced with high affinity from a greater proportion of sites than ICI 118,551 and IPS 339 (selective beta 2-adrenoceptor antagonists). In cerebellum, propranolol displaced both radioligands with uniform affinity. ICI 118,551 displaced with high affinity from a greater proportion of sites than CGP 20712A. The density of total beta-adrenoceptors (defined with isoprenaline) and of beta 1- and beta 2-adrenoceptors (defined with CGP 20712A and ICI 118,551 respectively) was studied by saturation binding of both radioligands in 13 brain areas. beta-Adrenoceptor density was higher in caudate, putamen and nucleus accumbens (100-120 fmol/mg protein) than cortex (50-70 fmol/mg protein) and densities were lowest in hypothalamus and cerebellum (27-38 fmol/mg protein). The proportion of beta 1-adrenoceptors (as a % of total beta-adrenoceptors) was high in caudate (80%), putamen (80%) and cortex (60-70%) and lower in hippocampus (40%) and cerebellum (30%). Both radioligands labelled a very similar number of beta-adrenoceptors in all brain regions studied.

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A "cavity" lesion made by aspiration in the rat occipital cortex induces a parenchymal and a vascular reaction in its vicinity. The first was mainly characterized by cellular necrosis and gliosis, the second by an increase of the vascular network. In vehicle treated rats, a 50% significant increase of the vascular network was observed around the cavity 4 days after the lesion, in comparison to the uninjured contralateral cortex. The effects of a vasoactive substance, suloctidil, on the vascular reaction was studied in the brain cortex. A single oral dose of suloctidil (30 mg/kg; 2 hours before the sacrifice) gave the same effect as the vehicle group. After 8 days of suloctidil oral administration (30 mg/kg; twice daily: 4 days before lesion and 4 days after) a significant increase (123%) of the vascular network was observed around the cavity. The hypothetical ways by which a chronic treatment of suloctidil induces this increase of the neovascularization observed after cortical lesion are discussed.

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Liquid collected from silicone impermeable sciatic regeneration chambers, fetal calf serum (FCS) and rat serum at different dilutions were tested on fibroblasts originating from hearts of newborn rats. The lower liquid dilutions presented a toxic effect. This effect was not counteracted by simultaneous addition of FCS at the same dilution. No evidence of a trophic activity was found in the liquid.

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Cortex, hippocampus, septum and striatum of day 18 rat embryos were grafted to several brain regions of young adult rats which had been lesioned in the chosen area 4 days earlier. Thirty days after transplantation, the grafts were fixed and morphometrically analysed under light microscope. The volumes, neuronal densities and total number of neurons of the transplants were compared. Each graft survived best when transplanted to its original region. Good survival was also achieved by heterotopic grafts between regions that are anatomically related. Striatal grafts showed reasonable survival only when transplanted to their original site. In a second series of experiences, the neurons from the same embryonic brain regions were cultured in a defined medium, to which was added tissue extracts from the lesioned regions of the adult brain. The neuronal survival was estimated. The in vitro results are closely related to those obtained in vivo. This experimental evidence agrees with the theory of the existence of a retrograde transport of NGF from the hippocampus to the septum, sustaining the survival of the latter. On the other hand, our results demonstrate the existence of other unidentified neurotrophic factors in the central nervous system which differ from one region to another.

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The purpose of this study is to validate a method for the quantification of the neovascularization in the vicinity of a lesion made in the cerebral rat cortex. A cavity, made by aspiration in the occipital cortex of young rats, induces around the lesion a parenchymal and vascular reaction. The parenchymal reaction is characterized by cellular necrosis and gliosis. The vascularization is more dense around the cavity than in normal cortex. Morphometric analysis indicates, 8 days after the lesion, a 130% increase of the total length of the vessels in comparison to the contralateral normal cortex.

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