Silicon microprotrusions with tailored chirality enabled by direct femtosecond laser ablation.

Here, we report on formation of nanoprotrusions on the surface of a bulk crystalline silicon wafer under femtosecond-laser ablation with a donut-shaped laser beam. By breaking circular symmetry of the irradiating donut-shaped fs-pulse beam, a switch in geometry of the formed surface nanoprotrusions from regular to chiral was demonstrated. The chirality of the obtained Si nanostructures was promoted with an asymmetry degree of the laser beam. An uneven helical flow of laser-melted Si caused by asymmetry of the initial intensity and temperature pattern on the laser-irradiated Si surface explains this phenomenon. Chirality of the formed protrusions was confirmed by visualizing cross-sectional cuts produced by focused ion beam milling as well as Raman activity of these structures probed by circularly polarized light with opposite handedness. Our results open a pathway towards easy-to-implement inexpensive fabrication of chiral all-dielectric nanostructures for advanced nanophotonic applications and sensing of chiral molecules.

Fractal energy spectrum of a polariton gas in a Fibonacci quasiperiodic potential.

We report on the study of a polariton gas confined in a quasiperiodic one-dimensional cavity, described by a Fibonacci sequence. Imaging the polariton modes both in real and reciprocal space, we observe features characteristic of their fractal energy spectrum such as the opening of minigaps obeying the gap labeling theorem and log-periodic oscillations of the integrated density of states. These observations are accurately reproduced solving an effective 1D Schrödinger equation, illustrating the potential of cavity polaritons as a quantum simulator in complex topological geometries.

Laser-Induced Periodic Surface Structures on Layered GaSe Crystals: Structural Coloring and Infrared Antireflection.

We study structural and morphological transformations caused by multipulse femtosecond-laser exposure of Bridgman-grown ϵ-phase GaSe crystals, a van der Waals semiconductor promising for nonlinear optics and optoelectronics. We unveil, for the first time, the laser-driven self-organization regimes in GaSe allowing the formation of regular laser-induced periodic surface structures (LIPSSs) that originate from interference of the incident radiation and interface surface plasmon waves. LIPSSs formation causes transformation of the near-surface layer to amorphous Ga2Se3 at negligible oxidation levels, evidenced from comprehensive structural characterization. LIPSSs imprinted on both output crystal facets provide a 1.2-fold increase of the near-IR transmittance, while the ability to control local periodicity by processing parameters enables multilevel structural color marking of the crystal surface. Our studies highlight direct fs-laser patterning as a multipurpose application-ready technology for precise nanostructuring of promising van der Waals semiconductors, whose layered structure restricts application of common nanofabrication approaches.

Reduced expression of G protein-coupled receptor kinases in schizophrenia but not in schizoaffective disorder.

Alterations of multiple G protein-mediated signaling pathways are detected in schizophrenia. G protein-coupled receptor kinases (GRKs) and arrestins terminate signaling by G protein-coupled receptors exerting a powerful influence on receptor functions. Modifications of arrestin and/or GRKs expression may contribute to schizophrenia pathology. Cortical expression of arrestins and GRKs was measured postmortem in control and subjects with schizophrenia or schizoaffective disorder. Additionally, arrestin/GRK expression was determined in elderly patients with schizophrenia and age-matched control. Patients with schizophrenia, but not schizoaffective disorder, displayed a reduced concentration of arrestin and GRK mRNAs and GRK3 protein. Arrestins and GRK significantly decreased with age. In elderly patients, GRK6 was reduced, with other GRKs and arrestins unchanged. A reduced cortical concentration of GRKs in schizophrenia (resembling that in aging) may result in altered G protein-dependent signaling, thus contributing to prefrontal deficits in schizophrenia. The data suggest distinct molecular mechanisms underlying schizophrenia and schizoaffective disorder.

Dielectric barrier discharges in analytical chemistry.

The present review reflects the importance of dielectric barrier discharges in analytical chemistry. Special about this discharge is-and in contrast to usual discharges with direct current-that the plasma is separated from one or two electrodes by a dielectric barrier. This gives rise to two main features of the dielectric barrier discharges; it can serve as dissociation and excitation device and as ionization mechanism, respectively. The article portrays the various application fields for dielectric barrier discharges in analytical chemistry, for example the use for elemental detection with optical spectrometry or as ionization source for mass spectrometry. Besides the introduction of different kinds of dielectric barrier discharges used for analytical chemistry from the literature, a clear and concise classification of dielectric barrier discharges into capacitively coupled discharges is provided followed by an overview about the characteristics of a dielectric barrier discharge concerning discharge properties and the ignition mechanism.

Arrestins as multi-functional signaling adaptors.

Arrestins are versatile regulators of cellular signaling expressed in every cell in the body. Arrestins bind active phosphorylated forms of their cognate G-protein-coupled receptors, shutting down G-protein activation and linking receptors to alternative signaling pathways. Arrestins directly interact with more than 20 surprisingly diverse proteins, such as several Src family kinases, ubiquitin ligases, protein phosphatases, microtubules, etc., and serve as scaffolds facilitating signaling in two MAP kinase cascades, leading to the activation of ERK1/2 and JNK3. A number of arrestin-binding partners are key players in signaling pathways that regulate cell proliferation, survival, and apoptotic death, which make arrestin interactions with these proteins inviting targets for therapeutic intervention. For example, enhancement of pro-survival or pro-apoptotic arrestin-dependent signaling is a promising strategy in treating disorders such as neurodegenerative diseases or cancer, respectively. Recent studies show that in the cell arrestin exists in at least three distinct conformations, free, receptor-bound, and microtubule-bound, with very different signaling capabilities. Precise identification of arrestin elements mediating its interactions with each partner and elucidation of conformational dependence of these interactions will pave the way to the development of molecular tools for targeted enhancement or attenuation of arrestin interactions with individual partners. This structural information is necessary to devise conventional drug-based approaches and to engineer specialized "designer" arrestins that can compensate for defects in receptor regulation associated with congenital disorders and/or redirect arrestin-mediated signaling to desired pathways. Arrestins are at the crossroads of crucial pathways that determine cell fate and behavior. Therefore, targeted manipulation of arrestin-dependent signaling has an enormous therapeutic potential.

Characterization of azimuthal and radial velocity fields induced by rotors in flows with a low Reynolds number.

We theoretically and experimentally investigate the flow field that emerges from a rodlike microrotor rotating about its center in a nonaxisymmetric manner. A simple theoretical model is proposed that uses a superposition of two rotlets as a fundamental solution to the Stokes equation. The predictions of this model are compared to measurements of the azimuthal and radial microfluidic velocity field components that are induced by a rotor composed of fused microscopic spheres. The rotor is driven magnetically and the fluid flow is measured with the help of a probe particle fixed by an optical tweezer. We find considerable deviations of the mere azimuthal flow pattern induced by a single rotating sphere as it has been reported by Di Leonardo et al. [Phys. Rev. Lett. 96, 134502 (2006)]. Notably, the presence of a radial velocity component that manifests itself by an oscillation of the probe particle with twice the rotor frequency is observed. These findings open up a way to discuss possible radial transport in microfluidic devices.

Mesolimbic dopamine D3 receptors and use of antipsychotics in patients with schizophrenia. A postmortem study.

BACKGROUND: The pharmacological properties and distribution of a recently cloned member of the dopamine D2 receptor subfamily, the D3 receptor, has led directly to the hypothesis that it may be the target of antipsychotic action. METHODS: To quantify D3 receptors, we characterized the conditions for selective binding of the radioligand iodine 125-labeled (R)-trans-7-hydroxy-2-[N-propyl-N-(3'-iodo-2'-propenyl)-amino] tetralin ([125I]trans-7-OH-PIPAT) to the human D3 receptor. We then measured by quantitative autoradiography in postmortem tissue the concentration of D3 receptors in the caudal and rostral basal ganglia regions in patients with schizophrenia and control subjects. RESULTS: We found about 2-fold elevations in the number of D3 receptors in the basal ganglia and ventral forebrain of long-term hospitalized patients with schizophrenia who received no antipsychotic drugs for at least a month before death (n = 7) compared with matched control subjects (n = 15). Patients with schizophrenia receiving antipsychotic drugs less than 72 hours before death (n = 8) had levels similar to those of control subjects. There were no differences in the binding characteristics or affinity of [125I]trans-7-OH-PIPAT binding to D3 receptors between control subjects and patients with schizophrenia. CONCLUSION: In contrast to the previously detected elevation of D2 and D4 receptor levels in schizophrenia, elevation of D3 receptor levels in limbic striatum and its efferents observed in patients with schizophrenia may be reduced by antipsychotic drugs.

Pathogenesis of levodopa-induced dyskinesia: focus on D1 and D3 dopamine receptors.

Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa therapy for Parkinson's disease. Taking advantage of a monkey brain bank constituted to study the pathophysiology of levodopa-induced dyskinesia, we here report the changes affecting D1, D2 and D3 dopamine receptors within the striatum of four experimental groups of non-human primates: normal, parkinsonian, parkinsonian treated with levodopa without or with dyskinesia. We also report the possible role of arrestin and G protein-coupled receptor kinases.

Beyond traditional pharmacology: new tools and approaches.

Traditional pharmacology is defined as the science that deals with drugs and their actions. While small molecule drugs have clear advantages, there are many cases where they have proved to be ineffective, prone to unacceptable side effects, or where due to a particular disease aetiology they cannot possibly be effective. A dominant feature of the small molecule drugs is their single mindedness: they provide either continuous inhibition or continuous activation of the target. Because of that, these drugs tend to engage compensatory mechanisms leading to drug tolerance, drug resistance or, in some cases, sensitization and consequent loss of therapeutic efficacy over time and/or unwanted side effects. Here we discuss new and emerging therapeutic tools and approaches that have potential for treating the majority of disorders for which small molecules are either failing or cannot be developed. These new tools include biologics, such as recombinant hormones and antibodies, as well as approaches involving gene transfer (gene therapy and genome editing) and the introduction of specially designed self-replicating cells. It is clear that no single method is going to be a 'silver bullet', but collectively, these novel approaches hold promise for curing practically every disorder.

Alterations in the cortical serotonergic system in schizophrenia: a postmortem study.

Previous studies have suggested a disturbance in the cortical serotonergic (5-HT) system in schizophrenia; however, these studies have been confounded by suicide in the patients groups, which in itself is associated with alterations in the 5-HT system. In this study we characterized various components of the 5-HT system in 14 areas of the frontal and parietal cortex in tissue obtained at postmortem from aged chronically hospitalized nonsuicidal schizophrenics compared to age-matched controls. We found no differences between control and schizophrenic subjects in the density of 5-HT uptake sites or other markers of 5-HT innervation. In Brodmann areas 24 and 6 the concentration of 5-HT2A,C receptors was decreased in all schizophrenics regardless of their antipsychotic treatment history. In all other areas examined 5-HT2A,C receptor concentrations were dramatically decreased in schizophrenics patients on drugs at time of death, whereas those off drugs at death showed the same values as control subjects. The density of 5-HT1A receptors was increased in areas 24, 9a (caudal part of area 9), 44, and 6 in subjects with schizophrenia. Antipsychotic treatment did not appear to have a significant effect. Thus, the specific pattern of alterations in the 5-HT system in schizophrenia may depend on the patient population and on antemortem antipsychotic treatment. These data also provide evidence that regulation of the 5-HT2 receptor may be involved in antipsychotic action.

Dopamine D(3) receptor is selectively and transiently expressed in the developing whisker barrel cortex of the rat.

The rodent primary somatosensory cortex (SI) contains a map of the body surface, the most conspicuous part of which are "barrels," neuronal aggregates in layer IV that receive somatotopic projections from whiskers on the rodent's snout. We report that the D(3) dopamine receptor (D(3)R) is selectively and transiently expressed in SI during the first 2 weeks of postnatal development. D(3)R binding sites and mRNA overlap completely and are limited to layer IV of SI. D(3)R/mRNA are organized in a pattern corresponding to somatotopic representations of the body (e.g., whiskers, jaws, paws, etc.) with the highest expression in the barrel field. D(3) mRNA is first detected at postnatal day (P)4, increases rapidly until P7-10, and sharply decreases after P14. D(3)R binding sites are detectable at P6, peak at P14, and decline afterwards. D(1), D(2), D(4), or D(5) mRNAs display dissimilar expression pattern. D(1) mRNA is mostly confined to infragranular layers throughout the cortex. D(4) mRNA expression in layer IV rises by 4 weeks postnatal, when D(3)R expression is virtually undetectable. Quantitative analysis of D(3) mRNA expression demonstrates that the proportion of D(3) mRNA-positive cells decreases between P7 and P14, whereas mRNA concentration per cell remains stable. Moreover, D(3)R number continues to rise, whereas mRNA levels begin to decline. Thus, a process limiting D(3)R expression to fewer cells may occur that also induces changes in post-transcriptional regulation of D(3)R expression in remaining cells. These findings indicate that dopamine acting via D(3)R may play an important role in the development or function of the SI.

Comparison of [3H]paroxetine and [3H]cyanoimipramine for quantitative measurement of serotonin transporter sites in human brain.

Previous studies have demonstrated that [3H]paroxetine and [3H]cyanoimipramine ([3H]CN-IMI) are highly selective ligands for the serotonin (5-HT) transporter. Using membrane preparation from the putamen, we confirmed that in human brain [3H]paroxetine labeled with high affinity one class of site associated with the 5-HT transporter. [3H]CN-IMI labeled two classes of sites in human brain. The one displaceable by 5-HT and with high affinity to 5-HT uptake inhibitors accounts for about 60% of the [3H]CN-IMI binding and, presumably, is associated with the 5-HT transporter. From the competition experiments, citalopram was selected to define [3H]CN-IMI binding to the 5-HT transporter in tissue sections because of its high selectivity to 5-HT transporter sites. A good correlation of the regional distribution patterns for [3H]CN-IMI and [3H]paroxetine was found using quantitative autoradiography. However, [3H]paroxetine underestimated high concentrations of the 5-HT transporter comparing to [3H]CN-IMI. This is likely to be due to the higher specific activity of [3H]CN-IMI. There is a good correlation between the regional distribution of 5-HT transporter sites labeled with either [3H]paroxetine or [3H]CN-IMI and the density of serotonergic innervation. This suggests that the brain areas that receive numerous serotonergic afferents, such as the hypothalamus and basal forebrain, might be common targets of these antidepressant drugs. Pharmacologic similarity of the sites labeled by both ligands as well as their similar distribution in the brain suggests that both antidepressant drugs interact with the same protein, thereby eliciting a similar neurochemical response.

Distribution of dopamine D3 receptor expressing neurons in the human forebrain: comparison with D2 receptor expressing neurons.

The dopamine D2 and D3 receptors are members of the D2 subfamily that includes the D2, D3 and D4 receptor. In the rat, the D3 receptor exhibits a distribution restricted to mesolimbic regions with little overlap with the D2 receptor. Receptor binding and nonisotopic in situ hybridization were used to study the distribution of the D3 receptors and neurons positive for D3 mRNA in comparison to the D2 receptor/mRNA in subcortical regions of the human brain. D2 binding sites were detected in all brain areas studied, with the highest concentration found in the striatum followed by the nucleus accumbens, external segment of the globus pallidus, substantia nigra and ventral tegmental area, medial preoptic area and tuberomammillary nucleus of the hypothalamus. In most areas the presence of D2 receptor sites coincided with the presence of neurons positive for its mRNA. D3 binding sites and D3 mRNA positive neurons were most abundant in the limbic striatum and efferent structures, such as the nucleus accumbens, ventral striatum, substantia nigra, internal segment of the globus pallidus, anteroventral nucleus of the thalamus, and rostral pars reticulata of the substantia nigra. One important difference from the rat is that D3 receptors were virtually absent in the ventral tegmental area. D3 receptor and D3 mRNA positive neurons were observed in sensory, hormonal, and association regions such as the nucleus basalis, anteroventral, mediodorsal, and geniculate nuclei of the thalamus, mammillary nuclei, the basolateral, basomedial, and cortical nuclei of the amygdala. As revealed by simultaneous labeling for D3 and D2 mRNA, D3 mRNA was often expressed in D2 mRNA positive neurons. Neurons that solely expressed D2 mRNA were numerous and regionally widespread, whereas only occasional D3-positive-D2-negative cells were observed. The regions of relatively higher expression of the D3 receptor and its mRNA appeared linked through functional circuits, but co-expression of D2 and D3 mRNA suggests a functional convergence in many regions of the signals mediated by the two receptor subtypes.

Arrestin2 and arrestin3 are differentially expressed in the rat brain during postnatal development.

Arrestins are adaptor proteins involved in homologous desensitization and trafficking of G protein-coupled receptors. Arrestins bind to activated phosphorylated receptors thus precluding further signal transduction. Two subtypes of non-visual arrestins, arrestin2 and arrestin3, have been cloned. Recently, specificity of various receptors to arrestins and differences in kinetics of receptor desensitization mediated by arrestins have been demonstrated. Both arrestins are expressed in the rat brain. However, quantitative assessment of their expression and detailed distribution are lacking. Here, we used quantitative ribonuclease protection assay and western blot to measure arrestin2 and arrestin3 mRNA and protein in the rat brain during postnatal development. In situ hybridization histochemistry was employed to study the detailed distribution of arrestin mRNAs in the adult and developing brain. Both arrestins were expressed from birth in all regions studied. Arrestin2 mRNA levels increased with development until the 14th postnatal day and then decreased, whereas arrestin2 protein levels continued to rise. Arrestin3 mRNA was maximal in neonates and then decreased, while arrestin3 protein changed little. In newborns and adults, the concentration of arrestin2 mRNA was two- to three-fold higher than that of arrestin3. In neonates, the excess of the arrestin2 protein over arrestin3 was commensurate with the excess of the arrestin2 mRNA (three-fold) but in the adult, the ratio was much higher (10-20-fold). Each arrestin demonstrated a unique distribution, although in many areas there was overlap suggesting co-localization. Both arrestins were highly expressed in the cortex and hippocampus. Arrestin2 was abundant in the thalamus, particularly in the anterior, intralaminar, and midline nuclei, while arrestin3 was abundant in the medial habenular. Arrestin3 was relatively abundant in most hypothalamic nuclei and extended amygdala. In the developing brain, arrestin3 was highly expressed in the subventricular zone, whereas arrestin2 was more abundant in differentiated areas. Our data demonstrate that arrestin2 is the major arrestin subtype in the rat brain, although arrestin3 is expressed in specific cell populations including postnatal proliferative zones. Because each arrestin appears to mediate receptor desensitization in a specific way, different kinetics of trafficking of the same receptor should be expected in different cells due to varying arrestin2/arrestin3 ratios. Thus, the response of receptors to specific drugs stimulating or blocking these receptors may depend on complement of arrestins in their target cells.

Cloning and functional characterization of salamander rod and cone arrestins.

PURPOSE: To clone, localize, and determine functional binding characteristics of rod and cone arrestins from the retina of the tiger salamander (Ambystoma tigrinum). METHODS: Two arrestins from salamander retina were cloned on the basis of their homology to known arrestins from other species. The expression pattern of these arrestins (SalArr1 and SalArr2) in the retina was determined by immunocytochemistry and in situ hybridization. SalArr1 and SalArr2 were expressed and functionally characterized. RESULTS: Both immunocytochemistry and in situ hybridization show that SalArr1 and SalArr2 localized specifically to rod and cone photoreceptors, respectively. SalArr1 demonstrated a characteristic high selectivity for light-activated phosphorylated rhodopsin (P-Rh*) and significant species selectivity, binding preferentially to amphibian rhodopsin over bovine rhodopsin. Mutant constitutively active forms of SalArr1 demonstrated a 2- to 4-fold increase in P-Rh* binding (compared with wild-type protein) and an even more dramatic (up to 25-fold) increase in binding to unphosphorylated Rh* and dark P-Rh. Constitutively active SalArr1 mutants also showed a reduced specificity for amphibian rhodopsin. The ability of Escherichia coli-expressed SalArr1, SalArr2, and an SalArr1-3A (L369A,V370A,F371A) mutant to bind to frog Rh* and P-Rh* and to compete with tritiated SalArr1 for amphibian P-Rh* was compared. SalArr1 and its mutant form bound to amphibian P-Rh* with high affinity (Ki = 179 and 74 nM, respectively), whereas the affinity of SalArr2 for P-Rh* was substantially lower (Ki = 9.1 microM). CONCLUSIONS: SalArr1 and SalArr2 are salamander rod and cone arrestins, respectively. Crucial regulatory elements in SalArr1 are conserved and play functional roles similar to those of their counterparts in bovine rod arrestin. Rod and cone arrestins are relatively specific for their respective receptors.

The immune system, apoptosis and apoptosis-related proteins in human ovarian tumors (a review).

Our studies on the relationships among the lymphoid system, apoptosis and apoptosis-related proteins (ARP) in human ovarian benign cysts, borderline tumors, and carcinomas are reviewed and analyzed. Fas and Fas ligand are expressed in 50% to 80% of the epithelial cells in all studied tumors. Many bcl-2-positive tumor epithelial cells are seen in benign cysts and they disappear as tumorigenesis progresses, whereas p53 protein is found only in borderline tumors and in carcinomas. Many exceptions to the opinion that bcl-2 inhibits apoptosis and p53 promotes it are encountered. Bcl-2 is lacking in epithelial cells of mucoid tumors of all grades, and its absence does not stimulate their apoptosis. P53 protein is absent from most lymphocytes, macrophages and epithelial tumor cells, nevertheless, they undergo apoptosis. Indeed, in many tumors apoptosis is regulated without the participation of bcl-2 and p53. Different components of the immune system become active during different stages of tumor development. The weak reaction of T-cell killers and macrophages is typical in benign cysts. In borderline tumors, the activity of T-cell killers increases in the parenchyma, and that of T helpers and macrophages in the stroma. In carcinomas with high lymphoid infiltration, a strong reaction of macrophages and T cell killers in the tumoral parenchyma as well high reaction of T helpers and B lymphocytes in the stroma are typical. Apoptosis that should protect against tumor also stimulates apoptotic death of lymphocytes and macrophages, and this has catastrophic consequences, as seen in weakly infiltrated carcinomas. In conclusion, our studies indicate that during malignancy the major task of the immune system is curtailment and control of tumorigenesis.

Ontogeny of the dopamine D2 receptor mRNA expressing cells in the human hippocampal formation and temporal neocortex.

The study details the cellular expression of the dopamine D2 receptor mRNA in the human temporal lobe during prenatal development. At 13 embryonic weeks (E13) D2 mRNA was widely expressed in the temporal lobe. At this time point in the dentate gyrus D2 mRNA positive cells first appeared at the outer border of the granular layer and their number increased with development. The CA1 exhibited the highest level of D2 mRNA expression. By E19-25 the hippocampal formation underwent rapid morphological maturation. D2 mRNA expression became more uniform and dense in the ammonic subfield. At all ages the subiculum appeared more mature morphologically but less intensely stained for D2 mRNA than the ammonic fields. In the entorhinal cortex D2 mRNA expression was most conspicuous in the future layer II at all ages. In the temporal neocortex D2 mRNA-positive cells were detected in the subplate and cortical plate. Differentiation of the cortical plate was accompanied by concentration of D2 mRNA-positive cells in layer V. The most conspicuous cells expressing D2 mRNA were found in the marginal zone of all regions and resembled Cajal-Retzius cells in morphology and location. Density of putative Cajal-Retzius cells expressing D2 mRNA decreased with development. They all but disappeared from the hippocampal areas by mid gestation, but in the temporal neocortex occasional cells were seen even at term. Early and widespread but region and cell type specific expression of D2 receptor mRNA suggests an important role of this DA receptor subtype in prenatal development of the human temporal lobe.

D3 receptors and the actions of neuroleptics in the ventral striatopallidal system of schizophrenics.

The mesolimbic dopamine (DA) system and an important target receptor, the D3 receptor, have been implicated in schizophrenia. We have identified, using non-radioactive in situ hybridization histochemistry, that D3 mRNA-positive neurons are highly concentrated in the ventral striatum, efferents of the ventral striatum (globus pallidus internal, ventral palladium, substantia nigra pars reticulata), and in regions projecting to the ventral striatum (medial dorsal thalamus, nucleus basalis, extended amygdala). D3 receptors are also highly enriched in the "limbic" striatal-pallidal-thalamic loop, exhibiting segregation from the D2 receptor-enriched "motor loop." This supports data developed in rats showing that the D3 receptor is a target of the mesolimbic DA system that can modulate the limbic striatal-palladial-thalamic loop. However, D2 and D3 receptors and their mRNAs are co-localized in many sensory regions (lateral and medial geniculate nuclei, basolateral and basomedial amygdala, regions of thalamus), suggesting mechanisms of cross-talk. We have also demonstrated that there are 45% elevations in D3 receptor number in ventral striatal neurons and their striatopalladial targets in schizophrenics that is reduced by concurrent antipsychotic treatment. Chronic haloperidol treatment to rats for 6 months with a 2-month withdrawal does not result in elevated D3 receptor number. We hypothesize that antipsychotic treatment via D3 receptors returns balance to limbic efferents of the ventral striatum. We established that early neonatal damage to the nigrostriatal DA system in rats produces characteristic adaptations in the pre- and post-synaptic components of the mesolimbic DA system that can provide a model to explore regulation by antipsychotics. This includes elevated release of DA from the mesolimbic DA terminals, elevated D3 receptor mRNA in the Islands of Calleja and nucleus accumbens, and enhanced behavioral response to psychostimulants.

Dopamine D2 receptor mRNA is expressed in maturing neurons of the human hippocampal and subicular fields.

Pyramidal neurons of the adult and fetal hippocampus and subicular fields were shown to express D2 mRNA using non-radioactive in situ hybridization histochemistry. At the earliest developmental stages examined (embryonic week (E) 13), cell packing within the CA1 region is dense and immature neuroblasts express D2 mRNA at high levels, as do more mature pyramid-like neurons in the deep aspect of the pyramidal cell layer. With development (E19 and E24), cell packing density is reduced, maturing neurons of the pyramidal layer are prominently D2 mRNA positive, while the majority of immature cells lining the superficial layer are D2 mRNA negative. In Layer II of the presubiculum there is a high density of immature D2 mRNA negative cells at E13 with D2 mRNA positive cells located on the periphery of the clusters. By E24, the cells in the layer II clusters are larger, express D2 mRNA, and D2 mRNA negative cells are rarely observed. Thus, expression of D2 mRNA in humans is an early and permanent feature of pyramidal neurons of these regions.