Dopamine Receptors In Rat Brain Research Articles

Definition of the In-vivo Binding of [3H]Spiperone in Rat Brain Using Substituted Benzamide Drugs

The ability of some substituted benzamide drugs to define in-vivo the binding of [3H]spiperone to brain dopamine receptors in rats was assessed using behaviourally effective doses in comparison with haloperidol. As judged using haloperidol, [3H]spiperone identified dopamine receptors in the substantia nigra, striatum, tuberculum olfactorium and hypothalamus, but not in frontal cortex or nucleus accumbens. The substituted benzamide compounds alizapride, metoclopramide, clebopride and YM 09151-2 prevented the accumulation of [3H]spiperone in the substantia nigra, striatum, tuberculum olfactorium and hypothalamus. However, YM 09151-2 also caused displacement of [3H]spiperone accumulation in the nucleus accumbens and frontal cortex. (+/- )-Sulpiride, (+/- )-sultopride, amisulpiride and prosulpride all prevented the accumulation of [3H]spiperone in the hypothalamus but were ineffective in one or more of the other regions containing dopamine receptors defined by [3H]spiperone. The isomers of sulpiride and sultopride stereoselectively defined the accumulation of [3H]spiperone in dopamine containing brain regions. The (-)-isomers of both drugs prevented the accumulation of [3H]spiperone in the substantia nigra, striatum, tuberculum olfactorium and hypothalamus. In contrast, (+)-sulpiride and (+)-sultopride were ineffective. Selected substituted benzamide drugs can be used to define the interaction of ligands with dopamine receptors in-vivo. These substances may be useful in PET studies in man. The isomers of some substituted benzamine drugs may be used to define dopamine receptors in-vivo by enantiomeric selectivity.

Further evidence for the stimulation of rat brain dopamine receptors by a cyclic analogue of dopamine.

Further evidence for the stimulation of rat brain dopamine receptors by a cyclic analogue of dopamine.

Further evidence for the stimulation of rat brain dopamine receptors by ergometrine.

Journal Article Further evidence for the stimulation of rat brain dopamine receptors by ergometrine Get access G N Woodruff, G N Woodruff Department of Physiology and Biochemistry, University of Southampton, Medical & Biological Sciences Building, Bassett Crescent East, Southampton SO9 3TU, UK Search for other works by this author on: Oxford Academic Google Scholar A O Elkhawad, A O Elkhawad Department of Physiology and Biochemistry, University of Southampton, Medical & Biological Sciences Building, Bassett Crescent East, Southampton SO9 3TU, UK Search for other works by this author on: Oxford Academic Google Scholar A R Crossman A R Crossman Department of Physiology and Biochemistry, University of Southampton, Medical & Biological Sciences Building, Bassett Crescent East, Southampton SO9 3TU, UK Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 26, Issue 6, June 1974, Pages 455–456, https://doi.org/10.1111/j.2042-7158.1974.tb09313.x Published: 12 April 2011 Article history Received: 18 January 1974 Published: 12 April 2011

Striatal and extrastriatal microPET imaging of D2/D3 dopamine receptors in rat brain with [18F]fallypride and [18F]desmethoxyfallypride

In this study, we compared two different D(2/3) receptor ligands, [¹⁸F]fallypride and [¹⁸F]desmethoxyfallypride ([¹⁸F]DMFP) with respect to the duration of the scan, visualization of extrastriatal receptors, and binding potentials (BP(ND) ) in the rat brain. In addition, we studied the feasibility of using these tracers following a period of awake tracer uptake, during which the animal may perform a behavioral task. Male Sprague-Dawley rats were imaged with [¹⁸F]fallypride and with [¹⁸F]DMFP in four different studies using microPET. All scans were performed under isoflurane anesthesia. The first (test) and second (retest) study were 150-min baseline scans. No retest scans were performed with [¹⁸F]DMFP. A third study was a 60-min awake uptake of radiotracer followed by a 90-min scan. A fourth study was a 150-min competition scan with haloperidol (0.2 mg/kg) administered via tail vein at 90-min post-[¹⁸F]fallypride injection and 60-min post-[¹⁸F]DMFP. For the test-retest studies, BP(ND) was measured using both Logan noninvasive (LNI) method and the interval ratios (ITR) method. Cerebellum was used as a reference region. For the third study, the binding was measured only with the ITR method, and the results were compared to the baseline results. Studies showed that the average transient equilibrium time in the dorsal striatum (DSTR) was at 90 min for [¹⁸F]fallypride and 30 min for [¹⁸F]DMFP. The average BP(ND) for [¹⁸F]fallypride was 14.4 in DSTR, 6.8 in ventral striatum (VSTR), 1.3 in substantia nigra/ventral tegmental area (SN/VTA), 1.4 in colliculi (COL), and 1.5 in central gray area. In the case of [¹⁸F]DMFP, the average BP(ND) values were 2.2 in DSTR, 2.7 in VSTR, and 0.8 in SN/VTA. The haloperidol blockade showed detectable decrease in binding of both tracers in striatal regions with a faster displacement of [¹⁸F]DMFP. No significant changes in BP(ND) of [¹⁸F]fallypride due to the initial awake state of the animal were found, whereas BP(ND) of [¹⁸F]DMFP was significantly higher in the awake state compared to baseline. We were able to demonstrate that dynamic PET using MicroPET Inveon allows quantification of both striatal and extrastriatal [¹⁸F]fallypride binding in rats in vivo. Quantification of the striatal regions could be achieved with [¹⁸F]DMFP.

Differential subcellular distribution of rat brain dopamine receptors and subtype-specific redistribution induced by cocaine

We investigated the subcellular distribution of dopamine D 1, D 2 and D 5 receptor subtypes in rat frontal cortex, and examined whether psychostimulant-induced elevation of synaptic dopamine could alter the receptor distribution. Differential detergent solubilization and density gradient centrifugation were used to separate various subcellular fractions, followed by semi-quantitative determination of the relative abundance of specific receptor proteins in each fraction. D 1 receptors were predominantly localized to detergent-resistant membranes, and a portion of these receptors also floated on sucrose gradients. These properties are characteristic of proteins found in lipid rafts and caveolae. D 2 receptors exhibited variable distribution between cytoplasmic, detergent-soluble and detergent-resistant membrane fractions, yet were not present in buoyant membranes. Most D 5 receptor immunoreactivity was distributed into the cytoplasmic fraction, failing to sediment at forces up to 300,000 g, while the remainder was localized to detergent-soluble membranes in cortex. D 5 receptors were undetectable in detergent-resistant fractions or raft-like subdomains. Following daily cocaine administration for seven days, a significant portion of D 1 receptors translocated from detergent-resistant membranes to detergent-soluble membranes and the cytoplasmic fraction. The distributions of D 5 and D 2 receptor subtypes were not significantly altered by cocaine treatment. These data imply that D 5 receptors are predominantly cytoplasmic, D 2 receptors are diffusely distributed within the cell, whereas D 1 receptors are mostly localized to lipid rafts within the rat frontal cortex. Dopamine receptor subtype localization is susceptible to modulation by pharmacological manipulations that elevate synaptic dopamine, however the functional implications of such drug-induced receptor warrant further investigation.

Anxiolytic Properties of 1-Aryl-4-(phthalimidoalkyl)piperazines and Their Affinity to 5-HT1A Serotonin and D2 Dopamine Receptors

Established in the late 1980s, the important role of 5-HT1A receptors in the pathogenesis of anxiety states and depressions has stimulated extensive search for the corresponding selective ligands. Among the known compounds possessing a high affinity to 5-HT1A receptors, the most thoroughly studied are aryl(hetaryl)piperazine derivatives. Although many of these substances possess anxiolytic properties [1, 2], only buspirone and gepirone – partial agonists of 5-HT1A receptors – are now used in clinical practice. The main factors limiting administration of these drugs in clinics is their low bioaccessibility, large delay (sometimes up to 2 – 6 weeks [3, 4]) in the therapeutic effect, and relatively high affinity to adrenaline ( 1, 2, 2), dopamine (D2), and other CNS receptors [1, 2, 5 – 9]. The low selectivity of aryl(hetaryl)piperazines is explained by the fact that the 5-HT1A serotonin, D2 dopamine, and 1 adrenaline receptors are “evolutionarily” close and belong to the same superfamily of G-protein-conjugated receptors. Indeed, an analysis of the primary amino acid sequences confirms the highly homologous character of these receptors [1]. Nevertheless, some highly selective ligands to 5-HT1A receptors have been found, such as (S)-UH-301 [10] and WAY-100635 [11], which is evidence that there are significant distinctions in the structure of binding centers of the aforementioned receptor types. The search for and identification of specific structural features of buspirone analogs and determining their selectivity with respect to 5-HT1A receptors [8, 9] is important both for the synthesis of drugs producing selective therapeutic action and for the basic knowledge of ligand – receptor interactions. This work is aimed at the synthesis of phthalimidoalkylpiperazines with variable polymethylene spacer lengths and different aryl fragment structures, determination of their affinity to 5-HT1A serotonin and D2 dopamine receptors in rat brain, and a comparative study of the anxiolytic properties.

In vivo autoradiography of [ 3H]SCH 39166 in rat brain: selective displacement by D1/D5 antagonists

The purpose of this study was to examine the receptor occupancy of D1/D5 antagonists for D1-like dopamine receptors in rat brain using [ 3H]SCH 39166, a highly selective D1/D5 antagonist with low affinity for 5HT2 receptors. A single concentration of triated SCH 39166 was administered to rats, with or without competing doses of the D1/D5 antagonist SCH 23390 and unlabeled SCH 39166, the D2-like antagonists haloperidol or the 5-HT 2 antagonist ketanserin. The bound radioactivity in the cortex, striatum, nucleus accumbens and olfactory tubercle was then quantified using an in vivo autoradiographic procedure. The results indicated that [ 3H]SCH 39166 was dose dependently displaced by the D1/D5 antagonists in regions associated with both the nigro-striatal pathway and the mesolimbic dopamine pathway, particularly the nucleus accumbens. Neither haloperidol nor ketanserin displaced [ 3H]SCH 39166 in any of the regions examined. The data were compared with previously published data examining the in vivo binding of [ 3H]SCH 39166 in rat brain homogenates. The relative values obtained were comparable to values detected in rat brain homogenates after in vivo binding of [ 3H]SCH 39166.

Selective alkylatation of dopamine D 2 and D 4 receptors in rat brain by N-( p-isothiocyanatophenethyl)spiperone

Effects of the D 2-like receptor alkylating agent NIPS ( N-[ p-isothiocyanatophenethyl]spiperone) on dopamine receptors in rat brain were characterized by radioreceptor assays and quantitative autoradiography. NIPS alkylated D 2 and D 4 receptors concentration-dependently in brain sections and transfected cells. NIPS also alkylated both receptors dose-dependently in vivo, with no effect on dopamine D 1-like or serotonin 5-HT 2 receptors at a dose that occluded 75% of D 2 and D 4 receptors. Pretreatment with D 2-like receptor selective antagonist haloperidol completely blocked the effects of NIPS. The findings demonstrate that NIPS selectively alkylates D 2 and D 4 receptors, indicating its potential utility for studies of these receptors.

In vivo regulation of DOPA decarboxylase by dopamine receptors in rat brain.

To test the hypothesis that dopamine (DA) receptors influence cerebral DOPA-decarboxylase (DDC) activity in vivo, we used HPLC to measure the kinetics of the cerebral uptake and metabolism of [3H]DOPA in carbidopa-treated rats, and in rats also treated acutely with a DA receptor antagonist (flupenthixol, 2 mg/kg, intraperitoneally) or a DA receptor agonist (apomorphine, 200 microg/g, subcutaneously). The unidirectional blood-brain clearance of [3H]DOPA (K1DOPA, 0.030 mL g(-1) min(-1)) increased by 50% after flupenthixol. The magnitudes of the relative DDC activity (k3DOPA) in striatum (0.20 min(-1)), olfactory tubercle (0.11 min(-1)), and hypothalamus (0.15 min(-1)) of carbidopa-treated rats were doubled with flupenthixol, but cortical DDC activity was unaffected (0.02 min(-1)). Apomorphine reduced the magnitude of k3DOPA in striatum by 20%. The rate constant for catabolism of [3H]DA formed in brain (k7', monoamine oxidase [MAO] activity), which ranged from 0.025 min(-1) in striatum to 0.08 min(-1) in hypothalamus of carbidopa-treated rats, globally increased 2- to 4-fold after flupenthixol, and decreased to 0.003 min(-1) in striatum after apomorphine. These in vivo results confirm the claim that acute blockade of DA receptors with flupenthixol stimulates the synthesis of [3H]DA from [3H]DOPA, and that this [3H]DA is subject to accelerated catabolism. Conversely, activation of the DA receptors with apomorphine inhibits DDC activity and DA catabolism.

Use of positron emission tomography to measure the effects of nalmefene on D1 and D2 dopamine receptors in rat brain

Positron emission tomography (PET) has been used in humans and in non-human primates to image and measure radioligand binding to neuroreceptors. The present study evaluated the feasibility of performing high-resolution PET experiments in a rodent model to measure receptor kinetics. The effects of acute and chronic administration of the opioid antagonist, nalmefene, on the binding activity of [11C]SCH23390 and [11C]N-methylspiperone at D1 and D2 dopamine receptors, respectively, was investigated in the rat. The interaction between central opioid and dopaminergic systems has been the focus of much attention due to their interactive role in mediating reinforcement and locomotor activity. In the present study, adult male Sprague–Dawley rats received either a single injection of 10 mg/kg of nalmefene or control vehicle solution 1 h prior to the PET scan or were chronically administered 10 mg/kg/day of nalmefene or vehicle for 7 days by an osmotic minipump. Following acute administration of nalmefene, the binding potential of [11C]SCH23390 in the striatum was significantly increased. No changes in [11C]N-methylspiperone binding were found. Following chronic nalmefene administration, no significant change in either [11C]SCH23390 binding potential or [11C]N-methylspiperone binding was detected. These results suggest that nalmefene administration produces transient changes in the binding potential of D1-receptors in the striatum that are normalized after 1 week of steady-state administration.

Partial dopamine receptor agonists with different degrees of intrinsic activity within a series of 2-(4-aminophenyl)- N,N-dipropylethylamine derivatives: synthetic chemistry and structure-activity relationships

Summary A series of 2-(4-aminophenyl)- N,N -dipropylethylamine derivatives were synthesized and tested for in vivo intrinsic activity at brain dopamine receptors in the rat. Differences in the sensitivity of dopamine receptors pre- and post-synaptically in the reserpine-treated rat were used to estimate the intrinsic activity of the various compounds as dopamine receptor agonists. Thus, the ability of the compounds to antagonize reserpine-induced increase in neostriatal dopamine synthesis and the suppression of spontaneous locomotor activity were taken as pre-and post-synaptic indices, respectively. The compounds in the present series display a gradient of intrinsic activity depending on the substituents in the aromatic ring. The presence of an amino group or an appropriate acylamino group in the 4-position was found to be critical for the biological activity of these compounds as agonists or antagonists. The introduction of halogen or a trifluoromethyl group in the 3-position resulted in high intrinsic activity (ie, agonist activity). The incorporation of a methyl group in the 3-position or halogens in the 3,5-positions resulted in a gradual decrease in intrinsic activity at rat brain dopamine receptors resulting in a series of compounds ranging from a full agonist to dopamine receptor blockade.

Quantitative autoradiographic analysis of D 1 and D 2 dopamine receptors in rat brain in early and late pregnancy

This study examined the levels of D 1 and D 2 dopamine receptors in the rat brain during pregnancy, a physiologically unique and important naturally occurring state. We are particularly interested in changes in the dopamine receptor complement of the brain during pregnancy because these receptors might support some components of the immediate postpartum onset of normal maternal behavior. Quantitative in vitro receptor autoradiography was applied particularly focusing on brain areas that control maternal behavior. The D 1 dopamine receptor selective antagonist [ 3H]SCH23390 and the D 2 dopamine receptor selective antagonist [ 3H]spiperone were used as the ligands. We examined the levels of binding to D 1 and D 2 dopamine receptors in brains in females on day 2 (early pregnancy) and day 21 (late, but prepartum pregnancy) of pregnancy. In addition, brains from females on diestrus-1 and from males provided reference points to the existing literature. Late in pregnancy females had significantly 18–27% lower levels of binding to D 1 dopamine receptors in the lateral striatum, the medial striatum, and the nucleus accumbens when compared to all other groups. Late in pregnancy, females had also significantly 11–25% lower levels of binding to D 2 dopamine receptors in the lateral striatum, the anterior striatum, the nucleus accumbens and the olfactory tubercle compared to all other experimental groups. We examined all of the brain regions already established to be important for maternal behavior, and found that dopamine receptor binding changed across pregnancy only in one such region, the nucleus accumbens. Thus pregnancy, perhaps the hormones of pregnancy, reduces the levels of D 1 and D 2 dopamine receptors in the striatum, and the nucleus accumbens, but not in other brain regions.

Do Central Antiadrenergic Actions Contribute to the Atypical Properties of Clozapine?

Full neuropharmacological understanding of the atypical antipsychotic agent clozapine remains elusive. Antidopaminergic actions of most neuroleptics probably contribute to their antipsychotic benefits, but also to neurological side-effects. Clinical evidence of abnormalities of dopamine (DA) and serotonin (5-HT) in psychotic disorders is inconsistent, but there is substantial metabolic and post-mortem evidence for hyperactivity of noradrenaline (NA). Clozapine is only weakly antidopaminergic but is a potent antagonist at brain alpha 1-adrenergic, 5-HT2-serotonergic, and muscarinic receptors. Its apparent limbic-over-extrapyramidal neurophysiological selectivity can be mimicked by combining a typical neuroleptic with a central alpha 1 antagonist. Clozapine strongly upregulates alpha 1, but not DA, receptor abundance, and may supersensitise alpha 1 but not DA receptors in rat brain. Clozapine also selectively increases activity of NA neurons and metabolic turnover in NA more than DA areas of rat brain, and also increases NA, but not DA or 5-HT, metabolites in human CSF. Potential psychotropic effects of selective central antiadrenergic agents may deserve reconsideration.

The neutral endopeptidase-24.11 inhibitor SCH 34826 does not change opioid binding but reduces D 1 dopamine receptors in rat brain

The effect of repeated administration of the neutral endopeptidase-24.11 (NEP) inhibitor SCH 34826 on the kinetic properties of opioid and dopamine binding in the rat cerebral cortex and striatum was investigated. SCH 34826, given at 100 and 300 mg/kg orally twice a day for 14 days, did not alter either B max or K d for the μ, δ or κ opioid receptor type in the cortex, as measured by studying binding parameters for the μ-selective ligand [ 3H][D-Ala 2,Me-Phe 4,Gly(ol) 5]enkephalin (DAGO), the δ-selective ligand [ 3H][D-Pen 2, D-Pen 5]enkephalin (DPDPE) and the κ ligand [ 3H]ethylketazocine (EKC). SCH 34826 reduced significantly the number of D 1 dopamine receptors labeled with [ 3H]SCH 23390 in the striatum (B max was 90 and 84% of controls at 100 and 300 mg/kg, respectively). The number of D 2 receptors, measured by [ 3H]spiperone binding, was unaltered. The K d values for both receptor types were not affected. The data demonstrate that chronic inhibition of enkephalin degradation by SCH 34826 does not alter opioid receptors, whereas it reduces the number of D 1 receptors. These findings provide further support for the role of opioids in modulating central dopaminergic systems. As a reduction in the number of D 1 receptors is an effect common to antidepressant treatments, the antidepressant potential of NEP inhibitors should be investigated.

Effects of repeated injections of cocaine on D 1 and D 2 dopamine receptors in rat brain

In order to determine if chromine administration of cocaine produced long-lasting alterations in dopamine receptor binding, rats were treated with single daily injections of cocaine (0, 10 or 20 mg/kg) for 15 consecutive days and killed either 20 min or 2 weeks after the last injection. The density of D 1 binding sites in frontal cortex was either unchanged (10 mg/kg) or slightly increased (m20 mg/kg) 20 min after the last daily injection, but was decreased 2 weeked 2 weeks later. D 1 sites in striatum were decreased both immediately and 2 weeks after the injection regimen. Decrease in D 1 binding site density in nucleus accumbens were observed only immediately after last injection. In contrast to these effects on D 1 binding sites, D 2 binding sites were decreased in striatum and frontal cortex and increased in the nucleus accumbens 20 min after repeated cocaine, but were unaffected 2 weeks after repeated cocaine. Computer-assisted analysis of the saturation isotherms revealed that chronic administrations of cocaine did not affect the affinity (K d) of the radioligands used to label D 1 or D 2 sites. These findingd suggest that repeated administration of cocaine results in long-term decrease in D 1 binding sites in striatum and frontal sortex and transient decrease in D 2 binding sites. Furthermore, cocaine caused opposite, Transient effects on D 1 and D 2 site density in nucleus accumbens.

In vivo interaction of cabergoline with rat brain dopamine receptors labelled with [ 3H]N-n-propylnorapomorphine

Cabergoline is a potent dopaminergic agent that interacts with agonists and antagonists of dopamine receptors in vitro. We studied the binding of [ 3H]N-n-propylnorapomorphine ([ 3H]NPA) to dopamine receptors after i.v. and oral administration of cabergoline to determine whether cabergoline crosses the blood-brain barrier; bromocriptine was used as a reference drug. Cabergoline and/or its active metabolite(s) did cross the blood-brain barrier and reach dopamine receptors. Comparative time-course analysis of the regional inhibition of [ 3H]NPA binding showed that cabergoline was more potent than bromocriptine in inhibiting [ 3H]NPA binding and that it occupied the receptor for longer. These effects were observed in all areas of the rat brain studied (striatum, olfactory tubercles, adeno- and neurohypophysis, thalamus and hypothalamus). Further studies in the striatum and adenohypophysis showed that cabergoline receptor occupancy was dose-dependent and still detectable 72 h after i.v. administration of the drug. While cabergoline was more potent in the striatum than in the adenohypophysis when administered i.v., the reverse administration, as determined 1 and 8 h later.

P-346 - Neurochemical studies on contrai effect of Buflomedil. (II) Effect of Buflomedil on dopamine receptors in rat brain

P-346 - Neurochemical studies on contrai effect of Buflomedil. (II) Effect of Buflomedil on dopamine receptors in rat brain

Dopamine D-2 auto- and postsynaptic receptors in the nigrostriatal system of the rat brain: localization by quantitative autoradiography with [ 3H]sulpiride

In vitro receptor autoradiography with [ 3H]sulpiride (a selective D-2 antagonist) was used to assess the effect of 6-hydroxydopamine and ibotenic acid lesions of the caudate-putamen and substantia nigra pars compacta on D-2 dopamine receptors in rat brain. A marked reduction in [ 3H]sulpiride binding within the pars compacta of the substantia nigra resulted from lesions of the substantia nigra compacta with either toxin, while substantial reduction in binding within the caudate-putamen followed only ibotenate lesions of that structure. Since (−)sulpiride is a selective D-2 antagonist, these data confirm that autoreceptors on nigral DA neurons are of the D-2 type, while a portion of D-2 receptors in the caudate-putamen are postsynaptic on striatal neurons.

Quantitative autoradiographic localization of the D1 and D2 subtypes of dopamine receptors in rat brain

The distribution of D1 and D2 receptors was studied in coronal sections of rat brain, using quantitative autoradiography. D1 receptors were labeled with 1.8 nM 3H-SKF-83566 (a brominated analog of 3H-SCH-23390), while D2 receptors were labeled with 1.0 nM 3H-spiroperidol (3H-SPD). The binding of both ligands to sections from brain and from a homogenate of caudate putamen (CPu mash) reached equilibrium within 80 min at 37 degrees C. CPu mash provided a virtually unlimited number of homogeneous sections that contained a high density of both D1 and D2 receptors. Sections of CPu mash were used in competition studies that confirmed that the specific binding of 3H-SKF-83566 was selective for D1 receptors, and that the binding of 3H-SPD was selective for D2 receptors. Scatchard analysis of equilibrium binding of the 2 ligands in the CPu in horizontal sections of rat brain revealed Kd values of 1.1 +/- 0.07 nM for 3H-SKF-83566 and 0.7 +/- 0.09 nM for 3H-SPD. Studies of the distribution of D1 and D2 receptors were carried out in coronal sections of brains from 5 rats. D1 receptors were found throughout the forebrain and were present in greater density than were D2 receptors in all regions examined except the olfactory nerve layer. In the CPu, nucleus accumbens, and olfactory tubercle, the densities of D1 and D2 receptors were, respectively, approximately 2,500 and 600-800 fmol/mg protein. In the substantia nigra, the density of D1 receptors was approximately 2,500 fmol/mg protein in both the compacta and the reticulata, but the density of D2 receptors was 230 fmol/mg protein in the compacta and 70 fmol/mg protein in the reticulata. The ventral tegmental area contained only 90 fmol/mg protein of D1 receptors, and D2 receptors were undetectable. The entopeduncular nucleus, zona incerta, and region of the ventral internal capsule had densities of D1 receptors of 550-950 fmol/mg protein and D2 receptor densities of less than 100 fmol/mg protein. Densities of D1 and D2 receptors were, respectively, 2,700 and 900 fmol/mg protein in the choroid plexus. Knowledge of the differences in the relative distributions of D1 and D2 receptors in various brain regions may increase our understanding of the functions of brain dopaminergic systems and may aid in the development of new therapeutic approaches for neuropsychiatric disorders.

Effect of single and repeated doses of acrylamide and bis-acrylamide on glutathione-S-transferase and dopamine receptors in rat brain

The effect of single and repeated doses of acrylamide (a neurotoxin) and N,N'-methylene-bis-acrylamide (a non-neurotoxic analogue of acrylamide) on glutathione (GSH), glutathione-S-transferase (GST) and dopamine receptors has been studied in rat brain. In vitro, both acrylamide and bis-acrylamide decreased brain GSH content in a concentration-dependent manner. At equimillimolar concentrations (2-10 mM) bis-acrylamide was more effective than acrylamide in lowering GSH levels. In vitro, GST activity was also inhibited as a function of acrylamide concentration. A single dose of either acrylamide or bis-acrylamide depleted GSH content of rat brain in a concentration-dependent manner without inhibiting GST activity. Repeated administration of either acrylamide or bis-acrylamide in rats (50 mg/kg X 10 days) decreased GSH content in the brain but GST activity was inhibited only by acrylamide and not by bis-acrylamide. Single or repeated injections of acrylamide but not of bis-acrylamide increased brain dopamine receptors ([3H]spiroperidol binding) in a concentration-dependent manner.