Biomedical subjects

C A Altar

Publications and source records attributed to C A Altar.

At least 55 records · Page 3Linked to original sources

PubMed1992

Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues.

Vascular endothelial growth factor (VEGF) is a secreted heparin-binding mitogen; its growth-promoting activity is limited to vascular endothelial cells in vitro and VEGF also stimulates angiogenesis in vivo. To identify target cells for VEGF and investigate the potential physiological role of this factor, iodinated recombinant human VEGF (125I-rhVEGF) was used for in vitro ligand autoradiography on tissue sections from adult rats. 125I-rhVEGF exhibited saturable, displaceable binding to a single class of sites with high affinity and low capacity in all tissues and organs examined. Colocalization of 125I-rhVEGF binding with Factor VIII-like immunoreactivity demonstrated binding sites associated with vascular endothelial cells of both fenestrated and nonfenestrated microvessels and the endothelium of large vessels, while no displaceable binding was evident on nonendothelial cells. Specific binding was associated with quiescent as well as proliferating vessels. These findings support the hypothesis that VEGF plays a specific role in both the maintenance and in the induction of growth of vascular endothelial cells.

Animals↗

PubMed1991

Entorhinal cortex lesion or intrahippocampal colchicine injection increases peripheral type benzodiazepine binding sites in rat hippocampus.

The peripheral type benzodiazepine binding site (PTBBS) has been proposed to be a good marker for reactive glial cells following brain insults. In the present study, homogenate binding of 3H-Ro5-4864 and quantitative autoradiography of 3H-PK-11195 binding (two ligands for the PTBBS) were used to assess the distribution, time-course and extent of reactive gliosis in the hippocampus following deafferentation by unilateral entorhinal cortex lesion or neuronal death produced by intrahippocampal colchicine injection. Intrahippocampal colchicine injections produced a 3-fold increase in 3H-Ro5-4864 binding in the dentate gyrus within 2 days. This effect was doubled in animals pretreated with the lysosomal inhibitor chloroquine. Quantitative autoradiography of 3H-PK-11195 binding 1 or 2 weeks after colchicine injection indicated that the increase in binding was restricted to the dorsal hippocampus both rostrally and caudally and was present in the dentate gyrus and CA1. Following a unilateral electrolytic lesion of the entorhinal cortex, the binding of 3H-Ro5-4864 to homogenates of the dentate gyrus was doubled 18 h after the lesion, reached a maximum at 4 days post-lesion, and returned to control values by 2 months after the lesion. A transient increase in binding was also observed 2 and 4 days post-lesion in the dentate gyrus contralateral to the lesion side. Autoradiography of 3H-PK-11195 binding indicated that the increase in PTBBS following entorhinal cortex lesion was restricted to the molecular layer of the dentate gyrus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Receptor-mediated transport of human recombinant nerve growth factor from olfactory bulb to forebrain cholinergic nuclei.

Receptors for nerve growth factor are present in the olfactory bulb and in cholinergic nuclei that send projections to the olfactory bulb. The retrograde transport of 125I-labeled recombinant human nerve growth factor (rhNGF) was demonstrated in the rat 18 h following an injection of [125I]rhNGF into the left olfactory bulb. In each of six animals, [125I]rhNGF label was observed in the ipsilateral horizontal limb of the diagonal band and, in four of the 6 animals, in the vertical limb of the diagonal band. Label was not observed in any other brain region except within the injected olfactory bulb. The transport of label to the diagonal band was blocked by the injection of 170-fold greater concentration of unlabeled rhNGF. Emulsion autoradiography of hematoxylin/eosin counterstained sections revealed silver grains clustered over numerous cell profiles that resembled neurons. In contrast, cerebellar injections of [125I]rhNGF, with or without unlabeled rhNGF, did not label diagonal band neurons, nor the lateral vestibular or red nuclei, from which originate the primary cholinergic afferents to cerebellum. The receptor-dependent transport of NGF from olfactory bulb to forebrain cholinergic nuclei suggests that this projection, unlike pontomesencephalic cholinergic pathways, may be responsive to endogenous NGF or exogenously administered rhNGF.

Animals↗

PubMed1991

Recombinant human nerve growth factor is biologically active and labels novel high-affinity binding sites in rat brain.

Iodinated recombinant human nerve growth factor (125I-rhNGF) stimulated neurite formation in PC12 cell cultures with a half-maximal potency of 35-49 pg/ml, compared with 39-52 pg/ml for rhNGF. In quantitative ligand autoradiography, the in vitro equilibrium binding of 125I-rhNGF to brain sections showed a 10-fold regional variation in density and was saturable, reversible, and specifically displaced by up to 74% with rhNGF or murine NGF (muNGF). At equilibrium, 125I-rhNGF bound to these sites with high affinity (Kd 52-85 pM) and low capacity (Bmax less than or equal to 13.2 fmol/mg of protein). Calculation of 125I-rhNGF binding affinity by kinetic methods gave average Kd values of 24 and 31 pM. Computer-generated maps revealed binding in brain regions not identified previously with 125I-muNGF, including hippocampus; dentate gyrus; amygdala; paraventricular thalamus; frontal, parietal, occipital, and cingulate cortices; nucleus accumbens; olfactory tubercle; subiculum; pineal gland; and medial geniculate nucleus. NGF binding sites were distributed in a 2-fold increasing medial-lateral gradient in the caudate-putamen and a 2-fold lateral-medial gradient in the nucleus accumbens. 125I-rhNGF binding sites were also found in most areas labeled by 125I-muNGF, including the interpedunucular nucleus, cerebellum, forebrain cholinergic nuclei, caudoventral caudate-putamen, and trigeminal nerve nucleus. 125I-rhNGF binding sites were absent from areas replete with low-affinity NGF binding sites, including circumventricular organs, myelinated fiber bundles, and choroid plexus. The present analysis provides an anatomical differentiation of high-affinity 125I-rhNGF binding sites and greatly expands the number of brain structures that may respond to endogenous NGF or exogenously administered rhNGF.

Animals↗

PubMed1991

Nerve growth factor and the neostriatum.

1. The present review summarizes evidence describing the expression, immunoreactivity, binding, transport, development, aging, and functions of NGF in the mammalian neostriatum. 2. Neostriatal NGF binding sites and intrinsic cholinergic neurons are co-localized, increase at a similar rate during ontogeny, and are lost to an equal extent following age- or injury-induced loss of neostriatal neurons. 3. Exogenously administered NGF augments ChAT activity in the intact caudate-putamen, nucleus accumbens, and following mechanical or excitotoxin-induced cholinergic injury. NGF antibodies lower ChAT in the intact caudate-putamen. 4. Neostriatal cholinergic interneurons are lost in the aged rat but also in Alzheimer's disease, Parkinson's disease, supranuclear palsy, and Huntington's chorea. Future studies need to address the extent to which these losses result from an abbreviation of NGF production, binding, or transport and whether rhNGF administration may retard or reverse these cholinergic losses.

Animals↗

PubMed1991

Suppression of in vivo neostriatal acetylcholine release by vesamicol: evidence for a functional role of vesamicol receptors in brain.

Experiments examined the effects of peripheral and central administration of the vesicular acetylcholine transport blocker vesamicol (AH5183) on the content, synthesis, and release of acetylcholine in the rat brain in vivo. In time course studies, a single intraperitoneal dose of DL-vesamicol (5 mg/kg) rapidly and reversibly (within 2 h) doubled the content of acetylcholine in the striatum and hippocampus, without affecting choline levels or the rate of transmitter synthesis. In microdialysis experiments, the same peripheral dose of drug produced a reversible 55% reduction in endogenous striatal acetylcholine release. A similar inhibitory effect was produced by direct intrastriatal perfusion with vesamicol. Moreover, this effect of vesamicol was (a) concentration-dependent and saturable (EC50 = 68 nM), (b) rapidly reversible, (c) stereospecific for the L-isomer, and (d) poorly mimicked by a vesamicol analog with lower plasma membrane permeability. This profile of effects is consistent with an interaction with a specific vesamicol receptor as defined by previous in vitro binding studies. These results support a functional role for vesamicol receptors in modulating central cholinergic transmission in vivo.

Acetylcholine↗

PubMed1991

Medial-to-lateral gradient of neostriatal NGF receptors: relationship to cholinergic neurons and NGF-like immunoreactivity.

High-affinity binding sites for recombinant human NGF (rhNGF) were studied in the caudate-putamen of the adult rat and rabbit. Displaceable 125I-rhNGF binding sites were densely distributed throughout the caudate-putamen and were 2-3-fold more prevalant in the ventrolateral and lateral than in the medial caudate-putamen. The amount of nondisplaceable binding did not vary throughout the caudate-putamen. The medial-to-lateral receptor gradient was correlated (r = +0.99) with a 2-3-fold medial-to-lateral increase in ChAT activity. In contrast, NGF-like immunoreactivity (NGF-LI) was prevalent but uniformly distributed in the caudate-putamen. Lesions of intrinsic cholinergic neurons by quinolinic acid produced extensive gliosis in the medial, central, and lateral caudate-putamen, yet 125I-rhNGF binding was decreased in each of these regions. The activity of ChAT and 125I-rhNGF binding throughout the caudate-putamen were each decreased by 40% following quinolinic acid. Binding was not changed after 70-77% dopamine nerve terminal depletions induced by 6-hydroxydopamine, demonstrating a nonglial, nondopaminergic locus for striatal NGF binding sites. The cholinergiclike topography of NGF binding sites throughout the intact caudate-putamen, the parallel decreases of cholinergic neurons and NGF binding sites following intrinsic neuronal loss, and the uniform neostriatal gradient of NGF-LI are consistent with the trophic role of endogenous NGF for cholinergic interneurons of the caudate-putamen.

Animals↗

PubMed1990

Discriminatory roles for D1 and D2 dopamine receptor subtypes in the in vivo control of neostriatal cyclic GMP.

The D1 and D2 subtypes of the dopamine receptor have been distinguished by their opposing effects on levels of neostriatal cyclic adenosine monophosphate (cAMP). The studies reported here show that the content of cyclic guanosine monophosphate (cGMP) in the mouse neostriatum is modulated by dopaminergic drugs in a manner which also discriminates D1 and D2 receptors. D1 receptor stimulation with SKF 38393 produced up to 90%, dose-related increases in neostriatal cGMP, whereas D1 antagonism with SCH 23390 decreased cGMP by 30% and blocked the increase induced by SKF 38393. D2 receptor stimulation with quinpirole did not alter cGMP levels whereas D2 antagonism increased cGMP by 40-60% after haloperidol and by up to 100% after sulpiride. The increases in neostriatal cGMP levels following D1 agonism were potentiated in an additive manner by haloperidol. Thus, neostriatal cGMP content is positively controlled by D1 agonism and negatively controlled by or unlinked to the D2 receptor. The reciprocal control of neostriatal cGMP levels by D1- and D2-selective compounds may contribute to the separate as well as combined actions of D1 and D2 ligands.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1990

Systemic injection of kainic acid: gliosis in olfactory and limbic brain regions quantified with [3H]PK 11195 binding autoradiography.

Neurodegenerative diseases may result from excessive stimulation of excitatory amino acid receptors by endogenous ligands. Because neuronal degeneration is associated with glial proliferation and hypertrophy, the degenerative changes throughout rat brain following the systemic administration of kainic acid (12 mg/kg) were mapped with quantitative autoradiography of [3H]PK 11195. This radioligand binds to a mitochondrial benzodiazepine binding site (MBBS) on microglia and astrocytes. Analysis of eight horizontal and four coronal brain levels revealed up to 16-fold increases in [3H]PK 11195 binding from 1 to 5 weeks but not 1 day after kainate injection. Increases in [3H]PK 11195 binding were predominantly in ventral limbic brain regions and olfactory projections to neocortical areas, with the olfactory cortex greater than subiculum/CA1 greater than anterior olfactory nucleus, medial thalamic nucleus, and piriform cortex greater than cingulate cortex and rostral hippocampus greater than dentate gyrus, septum, and amygdala greater than entorhinal cortex and temporal cortex. Little or no enhancement of [3H]PK 11195 binding was observed in numerous regions including the caudate-putamen, substantia nigra, nucleus accumbens, olfactory tubercle, cerebellum, thalamic nuclei, choroid plexus, medulla, parietal or occipital cortex, or pons. A 2-fold greater extent of neurodegeneration was obtained in ventral portions of the olfactory bulb, entorhinal cortex, temporal cortex, and dentate gyrus compared with the dorsal portions of these structures. The pattern of increase in [3H]PK 11195 binding closely matched the patterns of neuronal degeneration reported following parenteral kainate injection. These findings strengthen the notion that quantitative autoradiography of [3H]PK 11195 is a valuable tool to quantify the extent of neuronal degeneration. Furthermore, the quantitative changes in [3H]PK 11195 binding in different limbic structures parallel their relative variation in neuropathology observed in Alzheimer's disease but not Huntington's chorea. These findings are in agreement with the idea that excessive stimulation of excitatory amino receptors may contribute to the etiology of Alzheimer's disease.

Animals↗

PubMed1990

Regional distribution of alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid binding sites in rat brain: effect of chemical modification of SH- groups in tissue sections.

Previous studies have shown that chemical modifications of sulfhydryl (SH-) groups with mercurial compounds in rat brain membrane preparations increase the binding of alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid [(3H]AMPA), a ligand for the quisqualate/AMPA type of glutamate receptors. In the present study we investigated the regional distribution of SH- group modification by quantitative analysis of autoradiographic images of [3H]AMPA binding in tissue sections. We also compared the effect of SH- group modification to that of the chaotropic ion thiocyanate (SCN-) which has been generally utilized to study [3H]AMPA binding sites. Low levels of binding sites were observed in the absence of potassium thiocyanate (KSCN), with binding predominantly found in telencephalic structures. The presence of KSCN induced a relatively uniform and large (four- to fivefold) increase in binding throughout the different brain structures. Pretreatment of the tissue sections with the SH- group reagent p-chloromercuriphenylsulfonic acid produced a 0.5- to 1.5-fold increase in [3H]AMPA binding. The enhanced binding displayed a regional variation with the largest increase in binding observed in the outer layer of the parietal cortex whereas the lowest increase occurred in the striatum. These results indicate that SH- group modification of tissue sections produces an increase in [3H]AMPA binding similar to that observed in detergent-treated membrane preparations. Moreover they reveal that [3H]AMPA binding sites in different brain regions vary in their susceptibility to modification by SH- reagents, suggesting the existence in brain of a heterogeneous distribution of quisqualate/AMPA receptor subtypes.

4-Chloromercuribenzenesulfonate↗

PubMed1990

One year of continuous treatment with haloperidol or clozapine fails to induce a hypersensitive response of caudate putamen neurons to dopamine D1 and D2 receptor agonists.

In a "blind" experimental design, the sensitivity of caudate-putamen (CPu) cells to the selective dopamine (DA) D1 receptor agonist SKF-38393 and D2 receptor agonist LY171555 (quinpirole) in rats treated with either haloperidol (HAL), clozapine or tap water for 1 year was compared using the techniques of single cell recording and microiontophoresis. Although the maximum binding value for D2 receptors was elevated in chronic HAL-treated rats, there was no sign of electrophysiological supersensitivity of CPu neurons to the selective DA D1 and D2 receptor agonists. CPu cells were subsensitive to LY-171555 in HAL-treated rats without a drug withdrawal period. This suggests that residual HAL in the rat brain actively blocked the D2 DA receptors. In contrast, in clozapine-treated rats with or without a drug withdrawal period, the sensitivity of CPu cells to either the D1 or D2 agonists was not altered. Coadministration of SKF-38393 and LY-171555 onto the CPu neurons primarily produced an additive effect and only two cells both from the HAL group showed a synergistic action. The majority of CPu cells failed to respond to iontophoretic application of CCK-8S in either the control or antipsychotic drug-treated rats. If these findings can be extended to humans, they do not support the view that tardive dyskinesia is the result of CPu DA receptor supersensitivity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1989

Brain CCK-B receptors mediate the suppression of dopamine release by cholecystokinin.

The sulfated octapeptide of cholecystokinin (CCK-8S) and CCK fragments were administered to mice to determine the subtype and central versus peripheral location of the CCK receptor that modulates dopamine release in the neostriatum. Dopamine release was decreased when unsulfated CCK (CCK-8U) or the butoxycarbonyl tetrapeptide of CCK (t-boc-CCK-4) was infused into the brain ventricles but not when injected subcutaneously. These CCK fragments bind to the brain-type (CCK-B) but not alimentary-type (CCK-A) receptor. Centrally or peripherally administered CCK-8S also lowered dopamine release and this action was not blocked by the selective CCK-A receptor antagonist, L 364,718. The increase in dopamine release following amphetamine administration was attenuated by central injections of t-boc-CCK-4, CCK-8U, or CCK-8S, and this action of CCK-8S was not prevented by L 364,718. These data are the first to demonstrate that CCK-B receptors in brain mediate the suppression of dopamine release by cholecystokinin, especially when release is augmented. CCK-B receptor agonists should be useful for the treatment of psychiatric conditions that result from hyperactive dopamine neurons.

Amphetamines↗

PubMed1989

Preservation of dopamine release in the denervated striatum.

Dopamine metabolism and release were determined in the striata of rats sustaining varying damage to the nigrostriatal dopamine (DA) projection. DA metabolism, inferred from concentrations of dihydroxy-phenylacetic acid (DOPAC) or homovanillic acid (HVA), decreased with DA denervation of more than 20%. Dopamine release, inferred from the concentration of 3-methoxytyramine (3-MT), did not decrease unless the denervation was at least 80%. The amount of 3-MT per surviving neuron exceeded that for DOPAC over most of the denervation range. Thus, striatal DA release is preserved at normal levels with the survival of only 20% of the striatal DA innervation. Decreases in DA release, rather than decreases in DA metabolism or the density of dopamine innervation, coincide with the appearance of behavioral impairments.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1989

The dopamine autoreceptor agonist, (+/-)-trans-1,3,4,4a5,10b-hexahydro-4-propyl-2H [1]benzopyrano [3,4-b] pyridin-9-ol hydrochloride (CGS 15855A), modulates striatal dopamine metabolism and prolactin release.

The effects of apomorphine and the putative dopamine autoreceptor agonist, CGS 15855A, were evaluated in several functional assays that are modulated by pre- or post-synaptic D2 receptors. These included release of prolactin in vivo and in vitro from cultured lactotrophs; levels of dihydroxyphenylacetic acid (DOPAC) in the striatum; levels of acetylcholine (ACh); in the striatum and concentrations of cyclic guanosine monophosphate (cyclic GMP) in the cerebellum. The secretion of prolactin was inhibited by CGS 15855A in vitro and in vivo and which also decreased the levels of DOPAC in the striatum at doses 5-25 times less than those required to increase ACh in the striatum and levels of cGMP in the cerebellum. In contrast, apomorphine possessed a dose-ratio between 1.5 and 8.6 for these assay systems. These data suggest that CGS 15855A is a selective dopamine autoreceptor agonist which preferentially stimulates D2 receptors on lactotrophs and dopaminergic neurons as compared to D2 receptors on cholinergic interneurons in the striatum.

Animals↗

PubMed1989

Cholecystokinin receptor subtypes and neuromodulation.

The sulfated octapeptide of cholecystokinin (CCK-8S) and CCK fragments have been administered to mice to determine the subtype and location of the CCK receptor that modulates the release of dopamine (DA) in brain. 1. Centrally (i.c.v.) or peripherally (s.c.) administered CCK-8S lowers DA release, and to a lesser extent, metabolism, in the neostriatum and olfactory tubercle. 2. DA release is decreased when the CCK-B selective compounds, unsulfated CCK-8 (CCK-8U) or the butoxycarbonyl tetrapeptide of CCK (t-boc-CCK-4), are given i.c.v. but not when injected s.c. 3. The increase in DA release following amphetamine administration is attenuated by i.c.v. but not s.c. injections of t-boc-CCK-4 or CCK-8U and by CCK-8S given via either route. 4. None of the s.c. actions of CCK-8S are prevented by the CCK-A receptor antagonist, L 364,718. CCK-B receptors in brain mediate the suppression by CCK of basal and augmented DA release. CCK-B receptor agonists may be useful for the treatment of psychiatric conditions that result from excessive DA release.

Animals↗

PubMed1988

Cholecystokinin attenuates basal and drug-induced increases of limbic and striatal dopamine release.

Subcutaneous administration to mice of the sulfated octapeptide of cholecystokinin (CCK; 0.2-1 mg/kg) lowered dopamine release and metabolism in the caudate-putamen and frontal cortex in a dose- and time-related manner. Twelve-fold higher doses of CCK were required to lower dopamine release and metabolism in the olfactory tubercle. Amphetamine-induced increases in dopamine release but not metabolism in the caudate-putamen and olfactory tubercle were attenuated in a dose-related manner by CCK. Increases in dopamine release and metabolism following haloperidol were also attenuated by CCK. These data are consistent with the potential antipsychotic action of CCK receptor agonists. CCK appears to be a suppressor of striatal, limbic and cortical dopamine release, especially when release is augmented.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1988

[3H]vesamicol binding in brain: autoradiographic distribution, pharmacology, and effects of cholinergic lesions.

An autoradiographic analysis of high-affinity binding sites for the vesicular acetylcholine transport blocker [3H]vesamicol (2-(4-phenylpiperidino) cyclohexanol; AH 5183) was conducted in rat brain. [3H]Vesamicol binding was displaced 52-99% by DPPN [( 2,3,4,8]-decahydro-3-(4-phenyl-1-piperidinyl)-2-napthalenol) (IC50 = 14 nM) and by ketanserin (500 nM), haloperidol (43 nM), and vesamicol analogs, but not by drugs selective for adenosine, adrenergic, amino acid, calcium channel, monoaminergic, opioid, PCP, sigma, or several other receptor classes. [3H]Vesamicol binding was most concentrated in the interpeduncular nucleus and fifth and seventh cranial nerve nuclei. Moderate binding was found in the lateral caudate-putamen, medial nucleus accumbens, olfactory tubercle, vertical and horizontal diagonal bands of Broca, and basolateral amygdala. The distribution of [3H]vesamicol binding was similar to distributions of acetylcholine (r = 0.88), acetylcholine esterase (r = 0.97), choline acetyltransferase (ChAT) (r = 0.97), and [3H]hemicholinium-3 binding sites (r = 0.95-0.99). Lower correlations were obtained between [3H]vesamicol and muscarinic receptor densities (r = 0.50-0.70). Few exceptions to the match between binding and cholinergic neuronal markers were found, e.g., the molecular layer of the cerebellum and the thalamus. Lesions of cholinergic neuronal projections to the neocortex or hippocampus reduced [3H]vesamicol binding in each of these regions, but to a lesser extent than reductions in ChAT. [3H]Vesamicol binding sites appear to be anatomically associated with brain cholinergic neurons, a locus that is consistent with the control by this site of vesicular acetylcholine uptake.

Acetylcholine↗

PubMed1988

Dopamine neurochemical profile of atypical antipsychotics resembles that of D-1 antagonists.

The release and metabolism of dopamine in the mouse caudate-putamen were determined after the oral administration of antipsychotic drugs at doses equal to or sixfold greater than the ED50 dose for their inhibition of apomorphine-induced climbing. Dopamine release was equated with concentrations of 3-methoxytyramine (3-MT) and metabolism was equated with concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. Like the D-1 antagonists SCH 23390 and SKF 83566, most antipsychotic agents with an atypical preclinical profile suggestive of low extrapyramidal symptomatology (CGS 10746B, flumezapine, CL 77328, rimcazole, clozapine, RMI 81582, and fluperlapine) never increased dopamine release and produced variable increases in dopamine metabolism. Other atypical antipsychotics (thioridazine, mesoridazine, melperone) increased dopamine release at only one dose tested but increased dopamine metabolism at most doses. Antipsychotic agents associated with extrapyramidal side effects (setoperone, perlapine, haloperidol, chlorpromazine, and metoclopramide) increased dopamine release and metabolism at almost every dose tested. Thus, atypical antipsychotics increase the metabolism but not release of dopamine at behaviorally effective doses. The resemblance of these minimal effects on dopamine release to those obtained with D-1 antagonists that also have an atypical preclinical profile suggests that a mechanism related to D-1 receptor antagonism may contribute to the action of atypical antipsychotics.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗