Autoradiographic distribution of α2 adrenoceptors, NAIBS, and 5-HT1A receptors in human brain using [H]idazoxan and [H]rauwolscine

The regional distribution of [³H]idazoxan and [³H]rauwolscine was studied autoradiographically in human brain. [³H]Idazoxan binds with high affinity to α₂ adrenoceptors as well as to non-adrenergic sites (NAIBS). [³H]Rauwolscine, besides binding to α₂ adrenoceptors, also binds to 5-HT_1A receptors. Both radioligands labelled the same population of α₂ adrenoceptors, defined as the epinephrine-displaceable binding component. The highest densities of α₂ adrenoceptors occur in the leptomeninges, cerebral cortex and claustrum; lower densities were visualised in the basal ganglia, thalamus, pons, substantia nigra, cerebellum and medulla oblongata; no α₂ adrenoceptors were detected in amygdala and nucleus ruber. NAIBS were present in all the examined brain areas, with the highest densities found in the basal ganglia and substantia nigra. The finding that certain brain regions, such as the amygdala, contained NAIBS but no detectable α₂ adrenoceptors, suggests that the binding sites are independent from each other. The regional distribution of 5-HT_1A receptors labelled by [³H]rauwolscine is in agreement with previous studies using [³H]8-OH-DPAT.     

Specific bindings of prostaglandin D2, E2 and F2 alpha in postmortem human brain

Binding activities specific for each of [3H]prostaglandin (PG) D2, E2 and F2 alpha were detected in the P2 fraction of the human brain homogenates. The bindings were time-dependent, saturable and of high affinity; Kd values were 30 nM for all the PG bindings. Regional distribution of these binding activities was determined by measuring specific bindings with 10 nM [3H]PG-D2, [3H]PG-E2 and [3H]PG-F2 alpha in the P2 fractions from 17 brain regions. The PG-D2 binding activity was high in the hypothalamus, amygdala and hippocampus followed by cerebellar nuclei, thalamus, nucleus accumbens and cerebral cortex. The PG-E2 binding sites were similarly concentrated in the hypothalamus and the limbic system, but, unlike the PG-D2 binding, no significant binding of [3H]PG-E2 was observed in cerebellar nuclei, cerebellar cortex and putamen. Compared with these two PG bindings, PG-F2 alpha binding activity was low in many areas, but significant binding was detected in the amygdala, cingulate cortex, cerebellar medulla, hippocampus, nucleus accumbens, midbrain and hypothalamus. These results suggest the presence and specific distribution of three distinct types of PG binding activities, i.e. specific binding of PG-D2, PG-E2 and PG-F2 alpha, in the human brain.     

The formation and regional distribution of prostaglandins D2 and F2α in the brain of spontaneously convulsing gerbils

The distribution of the two major cycloxygenase products prostaglandin D₂ (PGD₂) and prostaglandin F_2α (PGF_2α) in 7 different regions of the brain (medulla, cerebellum, hypothalamus, striatum, midbrain, hippocampus and cerebral cortex) was studied. Basal levels were highest in hypothalamus and cortex. Following convulsions elicited by environmental stress prostaglandin concentrations increased in all areas, with largest increases (10–20-fold) in hippocampus and cortex, reaching 70 ng/g PGD₂ in hippocampus and 115 ng/g PGD₂ in cortex. These results demonstrate that, during spontaneous seizures, there is a greater increase in prostanoid production in those areas involved in the convulsive process.     

Quantitative light microscopic autoradiographic localization of α2-adrenoceptors in the human brain

In the present work the anatomical distribution of α₂-adrenoceptors in the human central nervous system was studied in detail by quantitative autoradiography using the selective α₂ agonist [³H]bromoxidine ([³H]UK-14304) as a ligand. Only postmortem tissues from subjects free of neurological disorders were used in this study. Very high or high densities of α₂-adrenoceptors were found along layers I and III in non-visual neocortex, layers III and IVc of the visual cortex, CA₁ field — stratum lacunosum-moleculare — and dentate gyrus — stratum granularis — at the hippocampal formation, nucleus arcuatus at the hypothalamus, locus ceruleus, nucleus dorsalis of vagus and at the stratum granularis of the cerebellar cortex. Relevant densities of α₂-adrenoceptors were also observed along the remaining layers of neocortex, nuclei centralis, medialis and corticalis at the amygdala, anterior thalamic group and rotundocellularis nuclei, paraventricular and ventromedial hypothalamic nuclei, substantia innominata, superior colliculus — stratum zonale — and lateral periaqueductal area at the midbrain, nucleus tractus solitarii and dorsal horn — substantia gelatinosa — of the spinal cord. [³H]Bromoxidine specific binding was very low or negligible in the remaining brain areas. Although a general parallelism between the distribution of these receptors could be observed for the rat and human brain, dramatic species differences in the level of α₂-receptors were found in several brain areas, such as thalamus, amygdala or cerebellar cortex. In general, the distribution of α₂-adrenoceptors in the human brain found here was parallel to that described for the noradrenergic presynaptic terminals in the mammalian central nervous system, lending some weight to the proposed predominant presynaptic localization of these receptors. The relevance of the anatomical distribution of α₂-adrenoceptors in the human brain for a better knowledge of the neurochemistry of neuropsychiatric disorders is discussed.     

Autoradiographic analysis of D1 and D2 dopaminergic receptors in rat brain after paradoxical sleep deprivation

Previous work had shown that paradoxical sleep deprivation (PSD) results in potentiation of several apomorphine-induced behaviors, leading to the suggestion that PSD induces an upregulation of brain dopamine receptors. In this study, quantitative receptor autoradiography was used to verify whether PSD does, in fact, induce alterations in D₁ or D₂ receptor binding, and to investigate the regional brain specificity of such effects. After 96 h of PSD, [³H]SCH-23390 binding to D₁ receptors was examined in 30 different brain areas of 10 experimental and 10 cage control rats. [³H]Spiperone was used to label D₂ sites in adjacent tissue sections. Results revealed a 39% increase in [³H]SCH 23390 binding in the entorhinal cortex of PSD rats (p < 0.05), but no other changes in any of the remaining 29 brain areas examined. In contrast, [³H]spiperone binding was significantly elevated in the n. accumbens (+45%) and in all subrogions of the caudate-putamen (range: +13% to +23%). These results, thus, provide evidence that PSD increases D₂ but not D₁ receptor binding in brain. The present results also suggest that upregulated D₂ receptors can account for the previously reported changes in apomorphine-induced behaviors after PSD.     

Specific increase of hypothalamic α1-adrenoceptors in spontaneously hypertensive rats: Effect of hypotensive drug treatment

To study potential central adrenoceptor alterations in the hypertension, we have determined α₁, α₂ and β-adrenoceptors using [³H]WB4101, [³H]yohimbine and [³H]DHA in the brain regions of spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP) and renal hypertensive rats. There was a significant increase in specific [³H]WB4101 binding only in the hypothalamus of SHR and SHRSP at 16–24 weeks of age compared to that of age-matched Wistar-Kyoto rats (WKY). Scatchard analysis revealed a 28–33% increase in the B_max value for hypothalamic [³H]WB4101 binding without a change in the K_d value, suggesting a change in the receptor density. An increased density of α₁-adrenoceptors was consistently observed in the prehypertensive (5 weeks) and developmental (10 weeks) stages of spontaneous hypertension. In contrast, there was no α₁-adrenoceptor alteration in the hypothalamus of rats with renal hypertension. The receptor alteration in the SHRSP hypothalamus was not abolished by a chronic hypotensive treatment which prevented the development of hypertension, thereby suggesting that an increased density of the α₁-adrenoceptors in spontaneous hypertension does not occur secondarily to the elevation of blood pressure. The SHRSP hypothalamus showed significantly lowered levels of noradrenaline. There was no change in specific binding of [³H]yohimbine and [³H]DHA in the brain regions of SHRSP, except the brainstem which showed a significant decrease in the [³H]yohimbine binding. Thus, the present study suggests an important role for hypothalamic α₁-adrenoceptors in the pathogenesis of spontaneous hypertension.     

Regulation of central α-adrenoceptors by serotoninergic denervation

α₁- and α₂-adrenoceptors were assessed by binding studies using [³H]prazosin and [³H]p-aminoclonidine as ligands in membrane preparations from the cortex, hippocampus and hypothalamus of rats, 3 weeks after intracerebroventricular injection of the neurotoxin 5,7-dihydroxytryptamine. Cortical α₁ and hippocampal α₂ adrenoceptors were significantly increased. Treatment also affected the affinity of cortical α₂ adrenoceptors. These results suggest a heterologous, region-specific regulation of both subtypes of central α-adrenergic receptors by serotonin.     

Central α1 adrenoceptor subtypes in narcolepsy-cataplexy: a disorder of REM sleep

The present study suggests the specific involvement within the central nervous system of an α₁ adrenoceptor subtype in a behavior, the control of cataplexy, a pathological analogue of rapid eye movement (REM) sleep atonia. Experiments have shown that prazosin, an α₁ antagonist, dramatically aggravates canine narcolepsy-cataplexy through a central mechanism, and that [ ³H]prazosin binding sites are increased in the amygdala of narcoleptic dogs¹⁶. However, the corresponding Scatchard plots were curvilinear and best fit was obtained with a two-site model, suggesting the existence of two [ ³H]prazosin binding sites¹⁸. These two sites (high and low affinity [ ³H]prazosin binding sites) met the criteria for authentic receptors and were respectively very similar to the α_1a an α_1b (high and low affinity for WB4101, respectively) subtypes recently described in the rat and rabbit. Our results of in vivo pharmacology and in vitro [ ³H]prazosin binding in canine narcolepsy now clearly implicate the low affinity [ ³H]prazosin binding site (α_b) in canine narcolepsy: (1) Prazosin, an α₁ antagonist with similar affinity for both subtypes, was much more potent in increasing cataplexy than WB4101, a compound with more affinity for the α_1a receptor. (2) Chlorethylclonidine and phenoxybenzamine, two irreversible blockers of the α₁ receptors with more affinity for the α_1b receptors, aggravate cataplexy for up to two weeks. (3) The α₁ receptor upregulation previously reported by our group in the amygdala of narcoleptic dogs was due to a selective increase in the low affinity [ ³H]prazosin binding sites. A role for noradrenaline in REM sleep regulation has been suspected for many years, but has never been clearly elucidated. Our data provide evidence for its specific involvement through a specific central α₁-adrenergic receptor subtype.     

Identification of extrastriatal dopamine D2 receptors in post mortem human brain with [I]epidepride

The regional distribution of striatal and extrastriatal dopamine D₂ receptors in human brain was studied in vitro with(S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-[¹²⁵I]iodo-2,3-dimethoxybenzamide, [¹²⁵I]epidepride, using post mortem brain specimens from six subjects. Scatchard analysis of the saturation equilibrium binding in twenty-three regions of post mortem brain revealed highest levels of binding in the caudate (16.5 pmol/g tissue) and putamen (16.6 pmol/g tissue) with lower levels seen in the globus pallidus (7.0 pmol/g tissue), nucleus accumbens (7.2 pmol/g tissue), hypothalamus (1.8 pmol/g tissue), pituitary (1.3 pmol/g tissue), substantia innominata (1.0 pmol/g tissue), and amygdala (0.87 pmol/g tissue). Of note was the presence of dopamine D₂ receptors in the four thalamic nuclei studied, i.e. anterior nucleus (1.0 pmol/g tissue), dorsomedial nucleus (0.96 pmol/g tissue), ventral nuclei (0.72 pmol/g tissue), and pulvinar (0.86 pmol/g tissue), at levels comparable to the amygdala (0.87 pmol/g tissue) and considerably higher than levels seen in anterior cingulate (0.26 pmol/g tissue) or anterior hippocampus (0.36 pmol/g tissue). The frontal cortex had very low levels of dopamine D₂ receptors (0.17–0.20 pmol/g tissue) while the inferior and medial temporal cortex had relatively higher levels (0.31–0.46 pmol/g tissue). Inhibition of [¹²⁵I]epidepride binding by a variety of neurotransmitter ligands to striatal, ventral thalamic and inferior temporal cortical homogenates demonstrated that [¹²⁵I]epidepride binding was potently inhibited only by dopamine D₂ ligands. The present study demonstrates that dopamine D₂ receptors are present in basal ganglia, many limbic regions, cortex and in the thalamus. The density of thalamic D₂ receptors is comparable to many limbic regions and is considerably higher than in cortex. Very few frontal lobe D₂ receptors are present in man.     

Autoradiographic mapping of 5-HT1B and 5-HT1D receptors in the post mortem human brain using [H]GR 125743

The distribution of 5-HT_1B and 5-HT_1D receptors in the human post mortem brain was examined using whole hemisphere autoradiography and the radioligand [³H]GR 125743. [³H]GR 125743 binding was highest in the substantia nigra and the globus pallidus. Lower levels were detected in the striatum, with the highest densities in the ventromedial parts. In the amygdala, the hippocampus, the septal region and the hypothalamus, lower [³H]GR 125743 binding was observed, reflecting low densities of 5-HT_1B/1D receptors. In the cerebral cortex, binding was similar in most regions, although restricted parts of the medial occipital cortex were markedly more densely labeled. Binding densities were very low in the cerebellar cortex and in the thalamus. Two methods were used to distinguish between the two receptor subtypes, the first using ketanserin to block 5-HT_1D receptors and the second using SB 224289 to inhibit 5-HT_1B receptor binding. The autoradiograms indicated that in the human brain, the 5-HT_1B receptor is much more abundant than the 5-HT_1D receptor, which seemed to occur only in low amounts mainly in the ventral pallidum. Although [³H]GR 125743 is a suitable radioligand to examine the distribution of 5-HT_1B receptors in the human brain in vitro, the selectivities of ketanserin and SB 224289 are not sufficiently high to give definite evidence for the occurrence of the 5-HT_1D receptor in the human brain.     

α2-Adrenoceptors in human forebrain: autoradiographic visualization and biochemical parameters using the agonist [H]UK-14304

The regional distribution and biochemical parameters ofα₂-adrenoceptors in post-mortem human brain tissue were analyzed in autoradiographic and membrane binding studies, using the full agonist, [³H]UK-14304. Autoradiographic visualization of these receptors in the forebrain revealed a heterogeneous anatomical distribution with high levels in the neocortex, ventral hypothalamus, hippocampus and some thalamic nuclei, among others. In membrane binding studies, analyses of saturation curves indicated the presence of a single population of sites for [³H]UK-14304 both in human and rat brain. There was a good correlation between the density of aα₂-adrenoceptors obtained by both procedures. [³H]UK-14304 is a feasible ligand to localise and quantifyα₂-adrenoceptors in human post-mortem material by autoradiographic and membrane binding techniques.     

Distribution of α-adrenergic, β-adrenergic and dopaminergic receptors in discrete hypothalamic areas of rat

Catecholamine receptor binding sites were measured in discrete hypothalamic nuclei or regions as well as in certain extrahypothalamic areas of the adult male rat. For each assay, discrete areas were microdissected from frozen tissue sections and pooled from several animals. Specific high affinity binding sites were assessed at fixed ligand concentrations for [³H]p-aminoclonidine (PAC) and [³H](2-C 2′,6′-(CH₃O)₂ phenoxyethylamino)-methylbenzodioxan (WB-4101) for α-adrenergic receptor sites, for [³H]dihydroalprenolol (DHA) for β-adrenergic receptor sites, and for [³H]2-amino-6, 7-dihydroxy-1,2,3,4-tetrahydronaphtalene (ADTN) and [³H]spiroperidol in the presence of cinanserin for dopaminergic receptor sites.Regional variations in [³H]WB-4101 binding were relatively small in magnitude, with most hypothalamic and extrahypothalamic areas possessing between 60 and 90% of the binding in frontal cortex. [³H]PAC binding showed a wider range of binding density across brain areas than did [³H]WB-4101, but, in general, variations in [³H]PAC binding paralleled those in [³H]WB-4101 binding. In hypothalamus, binding was characterized as being predominantly to α₁-receptors in the of [³H]WB-4101 and to α₂-receptors in the case of [³H]PAC. The medial hypothalamic areas exhibited a somewhat higher density of these α-adrenergic sites than did the lateral hypothalamus (perifornical hypothalamus and medial forebrain bundle). Also, the ratio of [³H]PAC to [³H]WB-4101 binding differed in different hypothalamic areas, ranging from 1.5:1 to 4:1. The median eminence was exceptional in that it contained appreciable [³H]PAC but no significant [³H]WB-4101 binding sites at the radioligand concentrations tested. Binding of [³H]DHA to β-adrenergic receptors varied over approximately a 3-fold range in the different hypothalamic areas, with binding highest in the medial forebrain bundle and the medial preoptic area, and lowest in the periventricular, dorsomedial and posterior hypothalamic nuclei, the median eminence and the zona incerta. The ratio of β-adrenergic to α-adrenergic binding sites was generally lower in the medial than in the lateral hypothalamic areas and higher in the extrahypothalamic areas examined than in the hypothalamus. With regard to [³H]spiroperidol and [³H]ADTN binding to dopaminergic sites, the striatum, nucleus accumbens and olfactory tubercle showed a greater density of [³H]spiroperidol than of [³H]ADTN sites, in contrast to the hypothalamus where [³H]ADTN binding was more predominant. Within the hypothalamus, [³H]ADTN binding was relatively uniform, while [³H]spiroperidol binding was quite high in four hypothalamic areas (lateral perifornical area, medial forebrain bundle, paraventricular and dorsomedial nuclei), intermediate in the median eminence and arcuate nucleus, and low or not detectable in all other hypothalamic areas.     

Canine narcolepsy is associated with an elevated number of α2-receptors in the locus coeruleus

α₂-Receptors in the canine brain were pharmacologically characterized using [³H]yohimbine binding. Competition studies revealed a single class of binding sites in frontal cortex but two distinct subtypes in nucleus caudatus. The role of central α₂-receptors in narcolepsy was investigated in 5 normal and 5 narcoleptic Doberman pinschers. Scatchard analysis of [³H]yohimbine binding in different brain areas revealed an increase in the number of α₂-binding sites limited to the locus coeruleus. This suggests that altered autoinhibition of norepinephrine release may be associated with the narcoleptic symptomatology.     

Alteration of alpha and muscarinic receptors in rat brain and heart following chronic nicotine treatment

Adrenergic and muscarinic binding sites in 4 brain regions (cerebral cortex, corpus striatum, hypothalamus/thalamus and brainstem) and in heart ventricles were measured in rats chronically treated with nicotine added to the drinking water in doses ranging from 6 to 8 mg/kg/day, for 4 weeks. Control rats received only tap water. The nicotine treatment led to increases in the specific binding of both [³H]prazosin and [³H]clonidine in the cerebral cortex. An increase in [³H]prazosin binding was also observed in the hypothalamus/thalamus of nicotine-treated rats. These changes were all due to an increase of about 23% in B_max. In the brainstem and heart left ventricle, respectively, an increase and a decrease in the affinity of [³H]quinuclidinyl benzilate binding were observed. There were no changes of the binding parameters for the 3 radioligands in other regions tested, and no alteration of [³H]dihydroalprenolol binding was detected in any region examined. These results indicate that chronic administration of nicotine causes an increase in the density of α₁-and α₂-binding sites in some brain regions and reciprocal changes of the affinity of muscarinic binding sites in the brain and in the heart.     

Changes of GABAA receptor binding and subunit mRNA level in rat brain by infusion of subtoxic dose of MK-801

In the present study, we have investigated the effects of prolonged inhibition of NMDA receptor by infusion of subtoxic dose of MK-801 to examine the modulation of GABA_A receptor binding and GABA_A receptor subunit mRNA level in rat brain. It has been reported that NMDA-selective glutamate receptor stimulation alters GABA_A receptor pharmacology in cerebellar granule neurons in vitro by altering the levels of selective subunit. However, we have investigated the effect of NMDA antagonist, MK-801, on GABA_A receptor binding characteristics in discrete brain regions by using autoradiographic and in situ hybridization techniques. The GABA_A receptor bindings were analyzed by quantitative autoradiography using [³H]muscimol, [³H]flunitrazepam, and [³⁵S]TBPS in rat brain slices. Rats were infused with MK-801 (1 pmol/10 μl per h, i.c.v.) for 7 days, through pre-implanted cannula by osmotic minipumps (Alzet, model 2ML). The levels of [³H]muscimol binding were highly elevated in almost all of brain regions including cortex, caudate putamen, thalamus, hippocampus, and cerebellum. However, the [³H]flunitrazepam binding and [³⁵S]TBPS binding were increased only in specific regions; the former level was increased in parts of the cortex, thalamus, and hippocampus, while the latter binding sites were only slightly elevated in parts of thalamus. The levels of β2-subunit were elevated in the frontal cortex, thalamus, hippocampus, brainstem, and cerebellar granule layers while the levels of β3-subunit were significantly decreased in the cortex, hippocampus, and cerebellar granule layers in MK-801-infused rats. The levels of α6- and δ-subunits, which are highly localized in the cerebellum, were increased in the cerebellar granule layer after MK-801 treatment. These results show that the prolonged suppression of NMDA receptor function by MK-801-infusion strongly elevates [³H]muscimol binding throughout the brain, increases regional [³H]flunitrazepam and [³⁵S]TBPS binding, and alters GABA_A receptor subunit mRNA levels in different directions. The chronic MK-801 treatment has differential effect on various GABA_A receptor subunits, which suggests involvement of differential regulatory mechanisms in interaction of NMDA receptor with the GABA receptors.     

Chemical lesion of the inferior olive reduces [I]Sarcosine–Angiotensin II binding to AT2 receptors in the cerebellar cortex of young rats

In young rats, AT₂ receptors and AT₂ receptor mRNA are discretely localized in neurons of the inferior olive, with highest expression in the medial nucleus. We previously detected AT₂ receptor binding, but not AT₂ receptor mRNA, in the molecular layer of the cerebellar cortex. To determine whether AT₂ receptors are expressed in climbing fiber terminals which arise to the molecular layer from the inferior olive and innervate Purkinje cells, we chemically destroyed olivary neurons of 2-week-old rats by intraperitoneal (i.p.) injection of the neurotoxin 3-acetylpyridine. Lesions of the inferior olive reduced [¹²⁵I]Sar¹–Ang II binding to AT₂ receptors and AT₂ receptor mRNA levels in this area by 50%, and produced a similar decrease in AT₂ receptor binding in the molecular layer of the cerebellar cortex. The extent of binding reduction was similar 3 days and 7 days after the lesion. 3-Acetylpyridine lesions did not change [¹²⁵I]Sar¹–Ang II binding to AT₁ receptors in the molecular layer of the cerebellar cortex or AT₁ receptor mRNA levels in Purkinje cells. AT₂ receptor binding and AT₂ receptor mRNA levels in the deep cerebellar nuclei were also not affected by 3-acetylpyridine. Our results support the hypothesis that AT₂ receptors are produced by inferior olivary neurons and transported through climbing fibers to the molecular layer of the cerebellar cortex. The high expression of AT₂ receptors in the inferior olivary–cerebellar pathway during a crucial time in postnatal development of climbing fiber-Purkinje cell connectivity suggest a role of AT₂ receptors in the development of this pathway.     

Distribution of α2 agonist binding sites in the rat and human central nervous system: Analysis of some functional, anatomic correlates of the pharmacologic effects of clonidine and related adrenergic agents

Using [³H]para-aminoclonidine, α₂ adrenergic binding sites have been mapped in the rat and human CNS using in vitro labeling autoradiographic techniques. In both the rat and human thoracic spinal cord, high densities of α₂ binding sites were associated with the substantia gelatinosa and the intermediolateral cell column. In the rat medulla, high binding site density was observed in the medial nucleus of the solitary tract, dorsal motor nucleus of the vagus, raphe pallidus and the substantia gelatinosa of the trigeminal nucleus, while lower levels of specific binding were found in the lateral and ventrolateral medulla. In the human, a similar distribution was observed. However, significantly lower levels of specific binding were seen in the medial nts as opposed to the dmv. In the rat, high levels of specific binding were seen at pontine and midbrain levels in the locus coeruleus, parabrachial nucleus and periaqueductal gray. In the forebrain, several hypothalmic and limbic regions, including the paraventricular and arcuate nuclei of the hypothalamus, the central, medial and basal nuclei of the amygdala, lateral septum and bed nucleus of the stria terminalis and pyriform, entorhinal and insular cortex were labeled. Each of these regions are involved in either modulating autonomic functions directly or integrating somatosensory and/or affective function with autonomic mechanisms. Further, these regions are interrelated by reciprocal connections, and neurons that utilize nor-adrenaline or adrenaline as their neurotransmitter form a vital part of these connections. Thus, these functional, anatomical and neurochemical correlates of the α₂ binding site distribution establish a neurological basis for the complex pharmacological effects of centrally acting α₂ agonists.     

Specific binding of [H]prostaglandin E2 to rat brain membranes and synaptosomes

There is saturable, reversible and specific binding for [3H]prostaglandin E2 (PGE2) to rat brain membranes. This binding is of high affinity, selectively distributed with a maximum in the hypothalamus, the amygdala and the posterior pituitary, and is associated subcellularly with the synaptosomal fraction. This specific PGE2 binding has the characteristics expected for receptors, so opening new perspectives which might clarify the role of PGs in the brain.     

Autoradiographic localization of α5 subunit-containing GABAA receptors in rat brain

Multiple subtypes of GABA_A receptors are expressed in the rat central nervous system (CNS). To determine the distribution and proportion of α5 subunit containing receptors, quantitative autoradiographic analyses were performed with both [³H]L-655,708 and [³H]Ro15-1788, an α5 selective and a non selective benzodiazepine binding site ligand, respectively. High densities of [³H]L-655,708 binding sites were observed in hippocampus and olfactory bulb, where α5 receptors accounted for 20–35% of total [³H]Ro15-1788 binding sites. Low levels of [³H]L-655,708 sites were associated with the cortex as well as amygdala, thalamic, hypothalamic and midbrain nuclei. These observations indicate that although [³H]L-655,708 binding sites have an overall low expression in rat CNS, they may contribute significantly to GABAergic inhibition in specific brain regions.     

Dopamine D1 and D2 receptor binding sites in brain samples from depressed suicides and controls

Dopamine D₁ and D₂ receptors were measured (by saturation binding of [³H]SCH23390 and [³H]raclopride) in caudate, putamen and nucleus accumbens, obtained at post-mortem from suicide victims with a firm retrospective diagnosis of depression and matched controls. There were no differences in the number or affinity of D₁ or D₂ receptors between suicides who had been free of antidepressants for at least three months prior to death, and controls. Increased numbers and decreased affinity of D₂ receptors were however found in each brain region of antidepressant-treated suicides. We argue that these increases are related to concurrent treatment with neuroleptics rather than a direct effect of antidepressants. Increased numbers of D₁ receptors in antidepressant-treated suicides were seen only in nucleus accumbens. This increase could not be clearly attributed to neuroleptics and may be related to antidepressant treatment.