DA Function Research Articles

D-1 receptor mediated modulation of the release of γ-aminobutyric acid by endogenous dopamine in the basal ganglia of the rat

1. 1. Presynaptic D 1 receptors are present on GABAergic terminals of neostriatal projections. 2. 2. By activating these receptors, exogenous dopamine enhances the release of GABA. 3. 3. Here the authors have explored whether endogenous dopamine was also able to activate the receptors, thus enhancing GABA release. 4. 4. The effect of methamphetamine, a dopamine releaser, on the release of tritiated GABA was studied in slices of substantia nigra pars reticulata, entopeduncular nucleus and caudate-putamen, targets of the striatal projections. 5. 5. Methamphetamine enhanced the release of the label. However the enhancement required an intact dopaminergic innervation, since it was lost in slices isolated from rats with 6-hydroxydopamine-induced lesions of the dopaminergic nigrostriatal system. 6. 6. The activation of the receptors by endogenous dopamine was also judged by the effect of the selective D 1 antagonist SCH 23390 in potassium depolarized slices. By preventing activation of the receptors by dopamine released as result of depolarization, the antagonist reduced GABA release. In 6-OHDA lesioned slices, no reduction was observed, even though the slices were also depolarized 7. 7. The results indicate that endogenous dopamine enhances GABA release from striatal terminals in the pars reticulata of the substantia nigra, entopeduncular nucleus and caudate-putamen. This would facilitate GABAergic neurotransmission. 8. 8. The study suggests that the function of DA in the basal ganglia is widespread, modulating not only the firing of the striatal efferent neurons but also the transmission of the fired impulses across synapses in the target nuclei of these neurons.

Interaction of CCKB receptors with amphetamine in responding for conditioned rewards.

Cholecystokinin (CCK) has been localized in the nucleus accumbens (NAC) where it may interact with dopamine neurotransmission. NAC dopamine is involved in the control over behavior produced by conditioned rewards. The present experiment tested the whether blockade of endogenous CCKB receptors with L-365,260 (0.1 mg/kg, IP) potentiates bar pressing for stimuli previously associated with food reward. Intra-accumbens amphetamine (20 micrograms) facilitated bar pressing for conditioned rewards. Systemic administration of L-365,260 potentiated this amphetamine response but produced no effect on responding when administered alone. These findings suggest that endogenous CCKB mechanisms may normally inhibit DA function in reward-related behaviors.

Evidence for the contribution of CCK B receptor mechanisms to individual differences in amphetamine-induced locomotion

Recent evidence shows that rats exhibit individual differences in their locomotor response to amphetamine (AMP). Moreover, evidence has accumulated showing that high-AMP responders exhibit more mesolimbic dopaminergic (DAergic) activation in response to AMP treatment than low-AMP responders. Cholecystokinin (CCK) is a peptide that is colocalised with mesolimbic DA and exerts complex modulatory actions on DA function. Two CCK receptor subtypes have been identified and selective antagonists have been developed. To examine the possible contribution of endogeneous CCK mechanisms to individual differences in responsivity to AMP treatment, male Wistar rats were divided into low- and high-AMP responders based on a mediam split of their locomotor response to AMP and the effects of the selective CCK antagonists L365-260 (CCK B; 0.01, 0.1, 0.5 mg/kg; n = 16) and devazepide (CCK A; 0.001, 0.01, 0.1 mg/kg; n = 23) were determined. Results showed that L365-260 (0.1 mg/kg) potentiated AMP-induced hyperactivity in low-AMP responders but did not affect AMP-induced hyperactivity in high-AMP responders. Devazepide was without effect in both groups of animals. This pattern of results suggests that CCK B, but not CCK A, receptor mechanisms contribute to interindividual. variation in responsivity to AMP.

The daughterless gene product in Drosophila is a nuclear protein that is broadly expressed throughout the organism during development

The daughterless (da) gene in Drosophila functions in the regulation of at least three significant developmental pathways: sex determination, neurogenesis and oogenesis. As a member of the helix-loop-helix (HLH) family of DNA binding proteins, the da gene product appears to act as a transcription factor. Based on the genetic and molecular characterization of da, it has been proposed that the da protein (Da) functions as a generic member of this family, serving throughout development as a necessary binding partner for an assortment of other HLH proteins. As a result of temporally and/or spatially restricted expression, these binding partners would provide some regulatory specificity to the functional transcription complex. In order to participate in this way in the regulation of multiple genes, Da must be expressed in numerous times and places during development. Using anti-Da antibodies, we validate two predictions of this scenario of Da function: (1) Da protein is not only nuclear localized, but also associated with chromosomes in vivo; and (2) Da protein is widely distributed, both spatially and temporally, throughout development. With regard to the essential role of maternal da + in progeny sex determination little, if any, Da protein is synthesized in the maternal germline. This suggests that the female-specific germline function of da + is provided to the zygote as maternally synthesized RNA that becomes translated early in embryogenesis.

Construction and accuracy analysis of images of the daily-mean mixed-layer depth

Abstract Using satellite data only, a unique model of the upper-ocean mixed-layer has been developed recently by Yan for calculating the thermal inertia (or the heat flux change per unit temperature change per day) of the mixed-layer from which daily mean mixed-layer depth is estimated. Thus digital maps of the oceanic daily mixed-layer depth in the vicinity of the Sargasso Sea for 14 May-30 August, 1982 have been generated from visible, near-infrared, thermal-infrared and microwave observations made by radiometers on board the NOAA-7, -8, GOES and Nimbus-7 satellites. The errors incurred in producing such maps are of two general type: measurement from satellites and model simplification. The sensitivity of the modelled mixed-layer depth to simplifications in the model (modelling errors) and to errors in data used for forcing the model (data errors) is considered here. To emph isize the oceanographic relevance of these errors, we express the errors in mixed-layer depth as a function of model errors and da...

Effects of systemically administered monoamine reuptake blocking agents on patterns of buspirone-induced analgesia in rats

We have recently shown the serotonin 5-HT 1A receptor agonist buspirone to produce analgesia in several pain tests in rats. As a 5-HT 1A agonist, buspirone may change serotonergic (5-HT) tone to alter the balance of central monoaminergic (MA) systems that function in analgesia. MA-reuptake blocking drugs have been shown to produce analgesia, both when given alone and in combination with a variety of other agents, presumably via their action upon MA neurochemistry. The present study was undertaken to examine the effect of systemic administration of the 5-HT-reuptake blocker amitriptyline (AMI: 10 mg/kg), NE-reuptake blocker desipramine (DMI: 10 mg/kg) or DA-reuptake blocker GBR-12909 (7.5 mg/kg) on patterns of analgesia produced by buspirone (1–5 mg/kg) in thermal and mechanical pain tests in rats. Neither reuptake blocking agents or buspirone, when administered alone or in combination, produced overt changes in motor activity at the doses tested. AMI alone was not analgesic in either thermal or mechanical pain tests. In both assays, AMI reduced the analgesic action of buspirone, with greater effects seen in the thermal test. When administered alone, DMI produced significant analgesia against thermal and mechanical pain. DMI significantly attenuated the analgesic action of all doses of buspirone in both pain tests. Alone, GBR-12909 did not affect nociception in thermal or mechanical tests. GBR-12909 decreased buspirone-induced analgesia at all doses in the thermal test, while having no effect on buspirone-induced analgesia against mechanical pain. These results demonstrate that facilitation of 5-HT, NE and DA function with reuptake blocking drugs did not enhance the analgesic action of buspirone. These data indicate against the adjuvant use of reuptake blocking compounds and buspirone as analgesics. Furthermore, such findings may suggest other possible non-MA substrates of buspirone-induced analgesia.

Natural convection in composite wall collectors with porous absorber

Steady natural convection heat transfer has been studied in a modified Trombe wall solar collector with a porous medium used as an absorber. The boundary conditions were: Two isothermal walls at different temperatures, two horizontal bounding adiabatic walls and either uniform or nonuniform heat generating porous layer with orifices. The aspect ratio A was from 5 to 10. The influence of orifice opening and position as well as the nonuniform heat generation within the porous medium have been studied in detail with the Darcy number varying from 10 −8 to 10 −2. The results are presented in terms of practical parameters (θ, θ max, q) as a function of Ra, Da and other nondimensional geometrical parameters. The isotherms and stream lines within the cavity are also produced. The overall results indicate that Da and geometrical parameters are the most important parameters affecting system performance.

Dopamine Receptor Subtypes and Arousal

Publisher Summary The study of events induced by centrally acting dopaminergic (DAergic) agents is a classic means of investigating the pharmacology and function of DA within the central nervous system (CNS). This chapter focuses on the activity of selective agonists for D-1 and D-2 receptors. The series of experiments demonstrates that DA receptor systems, especially the D-1 subtype, are primarily involved in the generation of arousal in laboratory animals. From the data, it appears that both D- 1 and D-2 receptors, when stimulated, can influence to different extents this physiological event. However, of the two receptors, D-1 seems more concerned with the generation of cortical and behavioral arousal. At the cellular level, the differential function in arousal process between D-1 and D-2 receptors might well depend on the different cascade of events that are initiated by the stimulation of each receptor site. The formation of the second messenger cAMP and the activation of the polyphosphoinositide system could certainly be responsible for differences in the ultimate biological response. In addition, it is well known that the DAergic system may be intimately related with the noradrenergic system in the control of behavior. Experimental and theoretical reviews have proposed that multicenter anatomical systems with multiple neurochemical signatures are involved in the elaboration of the sleep-waking states.

Excitatory amino acid treatment of the ventromedial globus pallidus enhances dopamine utilization in the prefrontal cortex of the rat via the thalamic mediodorsal nucleus.

Infusion of a low dose (5 microM) of the cell-selective chemical excitant quisqualic acid (QUIS) into rostral ventromedial globus pallidus (GP) had no immediate effect on DA utilization (assessed as [DOPAC]:[DA] and [HVA]:[DA] ratios) in either the medial bank of the prefrontal cortex (FCx) or the agranular insular cortex (AgCx). In contrast, a larger dose (630 microM) of another excitant sodium ibotenate (IBO) produced an immediate bilaterally symmetrical increase in both indices of DA utilization in FCx. There was also a marked trend towards a bilateral increase in these indices of DA utilization in AgCx. In order to determine whether these effects on cortical DA utilization are mediated by a direct cortical route or via the thalamic mediodorsal nucleus (lateral division, MDL), infusions of IBO into GP were repeated in animals with a 1-week-old N-methyl-D-aspartate lesion of MDL. The increase in DA utilization of FCx following infusion of IBO into GP was abolished, although the trend towards increased DA utilization in AgCx was still maintained. Since MDL innervates FCx but not AgCx and since we have previously shown that MDL lesions alone have no effect on DA utilization in either cortical region, the present results suggest that the changes in cortical DA utilization are probably mediated via MD. Thus in addition to the well-documented control exerted by the thalamus over brain DA function, this has now been extended in the present study to include GP, which projects both directly and indirectly to the thalamus.

Amygdala kindling modifies interhemispheric dopaminergic asymmetry

Brain dopamine is known to retard the development of kindled seizures, but it is uncertain whether kindling affects dopamine function. In the present study, rats were screened for cerebral dominance by recording their preferred direction of rotation when injected with d-amphetamine. Bipolar stimulating electrodes were then implanted in the amygdaloid complex of either the dominant or nondominant hemisphere (i.e., respectively, contra- and ipsilateral to the preferred direction of rotation; the dominant hemisphere identified in this way has been shown to contain higher concentrations of dopamine than the nondominant hemisphere). Kindling stimulation (or sham-kindling, in control rats) was applied through the electrodes two or three times daily for 21 days, and the rats were reassessed for amphetamine- and apomorphine-induced rotation, during and after the course of treatment. Kindling of the originally dominant hemisphere caused a diminution of rotational asymmetry as measured in tests 2 to 3 h after stimulation sessions, and in some rats led to a reversal in the preferred direction of amphetamine-induced rotation. Kindling of the nondominant hemisphere tended to accentuate the original amphetamine-induced asymmetry. The direction of rotation induced by a direct postsynaptic DA-receptor agonist (apomorphine) was not significantly affected by kindling of either hemisphere. It appears that kindling stimulation brings about a relatively inferior level of DA function on the stimulated vs. the nonstimulated side of the brain, and that this process depends mainly on changes occurring at a presynaptic level.

Neuroleptics, Dopamine, and Schizophrenia

Neuroleptic drugs have provided not only the most efficacious form of treatment for schizophrenia but also a unique pharmacologic probe for discerning its pathophysiology. The link between the antipsychotic effects of neuroleptics and dopamine systems continues to be supported by current research. Recent preclinical and clinical studies suggest that time-delayed changes in DA neuronal function may more closely relate to the therapeutic effects of neuroleptics than does their relatively immediate effect of DA receptor blockade. The use of levels of plasma HVA as a noninvasive reflector of DA function provides a research strategy for longitudinal studies of neuroleptic effects in schizophrenia. Preliminary evidence suggests that neuroleptic-induced changes in levels of plasma HVA may be of value as an in vivo marker for neuroleptic antipsychotic effects. The recent identification and characterization of the mesocortical DA system, which links the midbrain to frontal areas of the cerebral cortex, represents a significant development in the neurobiology of CNS DA systems. The behavioral implications of the functional neuroanatomy of the mesocortical system, its relative unresponsiveness to neuroleptic agents, and the possibility of modulatory effects on the mesolimbic DA system render the mesocortical system a particularly important area of research with etiologic and pharmacotherapeutic implications for schizophrenia. The accumulating evidence indicating structural brain abnormalities in a significant number of schizophrenic patients has renewed interest in classical neuropathologic approaches to understanding its etiology. Although current evidence does not uniformly support the hypothesis of two schizophrenia types reflecting DA and non-DA forms of the illness, the postulate is useful as an attempt to integrate recent findings into a conceptual framework. Better understanding of the biochemical basis for heterogeneity of neuroleptic response and systematic data relating this responsivity to morphologic brain changes constitute an important direction for schizophrenia research.

Choice of predicate and narrative manipulation: Functions of dearu and da in modern Japanese fiction

This paper examines the two forms of copula, dearu and da, in modern Japanese fictional discourse. While most previous studies suggest that these two forms differ in terms of style, this paper proposes that the choice between the dearu and da predicate is motivated by a narrative manipulation that is realized by the external and internal positioning the text-producer takes toward the narrative scene. Specifically, dearu is effective in expressing a conceptual view most frequently taken from the text-producer's position external to the scene and it usually constitutes a narrative discourse. Da, on the other hand, is effective in expressing a perceptual point of view frequently based on the text-producer's position internal to the scene and it commonly constitutes a direct discourse. Further, it is shown that this external/internal distinction is supported by syntactic evidence that da, but not dearu, can occur in so-called Genshoobun ‘sentence of immediate description’. This paper is an attempt to investigate occurrences of linguistic devices that are seemingly random in literary discourse from a discourse functional perspective.

Reactive capacity: A sensitive behavioral marker of movement initiation and nigrostriatal dopamine function

Thirty-two Long Evans male rats with sham operations or unilateral 6-OHDA-induced damage to meso-telencephalic dopaminergic neurons were evaluated on a reactive capacity task that demanded high speed movement initiation. The task required lever manipulation to avoid signalled shock. The interval between the warning and the shock was incrementally reduced. A one-sleeved vest provided the opportunity to measure movement initiation of each limb independently. Extent of lesion was assessed by [ 3H]DA uptake, [ 3H]spiroperidol binding, or DA levels. Movement initiation latencies for each forelimb were found to be linearly related to interhemispheric striatal DA asymmetry induced by microinjections of 6-OHDA. Even those lesions resulting in small to moderate decreases in DA function, including deficits causing no chronic posture or sensory asymmetries, resulted in reactive capacity deficits and greatly slowed reaction time in the paw contralateral to the lesion. Following severe lesions, small yet substantial deficits were also seen in ipsilateral paw performance, which may be related to DA depletions found in the non-lesioned striatum. Thus, a reactive capacity task which requires the animal to react with maximal speed appears to be a potentially good index of nigrostriatal dopamine integrity even when the depletion is not severe.

Cholecystokinin peptides, dopamine and schizophrenia — A review

1. CCK-IR is co-localized with DA in some DA neurons projecting to limbic structures. The extent of the co-localization is species dependent. The co-localization of CCK and DA is of interest in view of the DA hypothesis of schizophrenia and the putative role of limbic dysfunction in the pathophysiology of this disorder. 2. In animals biochemical, electrophysiological and behavioural studies point to an interaction between CCK and DA. Whereas some investigations point to an inhibitory effect on DA function, which would be compatible with a potential antischizophrenic action, others point to an enhancement or no effect. CCK peptides show a neuroleptlc-like profile in several screening tests for neuroleptics but not in all studies. 3. In man there is endocrinological evidence for an inhibitory effect of CCK-33 and CCK-8 on DA function. However, alternate explanations are possible. CSF CCK-IR is unchanged or decreased in schizophrenia. Autopsy investigations have shown significant decreases, increases or no change in brain CCK-IR concentrations and a decrease in CCK-33 binding in schizophrenia. Eight of 11 clinical trials with CER, CCK-8 or CCK-33 have shown a therapeutic effect in schizophrenia; only two of these eight trials have been double-blind studies. The three controlled investigations which have shown no effect have used only small patient populations. None of the trials have used an active placebo. 4. It is difficult to reconcile the apparent long duration of antipsychotic activity with the short half-life of the peptides and problems of the peptides in crossing the blood brain barrier. Despite these apparent anomalies information to date is sufficiently impressive to warrant further detailed investigation of CCK-DA-interactions and the evaluation of the clinical effects of a variety of CCK peptides and related compounds, natural and synthetic, which may more easily cross the blood brain barrier and which may show regional selectivity in site of action in brain.

Effects of unilateral microinjections of sulpiride into the medial prefrontal cortex on circling behavior of rats

1. Bilateral 6-OHDA lesions of rats' medial prefrontal cortex increased locomotor activity after 7–10 days suggesting that cortical DA may normally inhibit motor behaviour. However, hyperactivity may have resulted from enhanced subcortical DA function. 2. Acute manipulation of frontal cortical DA neurotransmission in the present experiment avoided lesion-induced subcortical changes. 3. Sulpiride (0, 6, 12, 24 ug in 1 ul) was Injected unilaterallv into the medial prefrontal cortex of rats pretreated with (+)-amphetamine (1.5 mg/kg i.p.). 4. Circling behavior was scored during four 5-min intervals of a 60-min test session which began with injections and placement in a flat, circular arena. 5. SUL resulted in ipslversive circling whereas its vehicle did not. These results were consistent with those seen with other DA drugs and suggest an excitatory influence of frontal cortical DA on locomotor activity.

Implications of the absolute magnitude distribution functions of DA and non-DA white dwarfs

view Abstract Citations (67) References (10) Co-Reads Similar Papers Volume Content Graphics Metrics Export Citation NASA/ADS Implications of the absolute magnitude distribution functions of DA and non-DA white dwarfs. Sion, E. M. Abstract The number distribution of absolute magnitudes in the sample of proper-motion-dominated white dwarfs of Liebert et al. (1983) and in the Palomar-Green sample is determined, and the distributions of DA and non-DA spectral types are analyzed on the basis of color-luminosity calibrations. The DA/non-DA ratios for the cool and hot ends of the distribution are found to be 2:1 and 6:1, respectively. Two mechanisms which can help explain the distribution functions are examined: a DA-to-DB transition at Te above 15,000 K via the diffusion-induced burning of surface H (as suggested by Michaud et al., 1984) and convective mixing of surface H in cooling DA stars at Te = 10,000-12,000 K. Publication: The Astrophysical Journal Pub Date: July 1984 DOI: 10.1086/162240 Bibcode: 1984ApJ...282..612S Keywords: Distribution Functions; Stellar Color; Stellar Evolution; Stellar Magnitude; Stellar Spectrophotometry; White Dwarf Stars; Balmer Series; Carbon; Helium; Iue; Astrophysics full text sources ADS | data products SIMBAD (1)

Estrogen potentiates the stereotypy induced by dopamine agonists in the rat

Repeated weekly treatment with 100 μg/kg of estradiol benzoate (EB) to ovariectomized female rats intensified the stereotypy induced by the dopamine agonists amphetamine and apomorphine. A similar effect on amphetamine-stereotypy was produced 48 hours after a single injection of 10 μg/kg of EB. The fact that EB failed to increase blood or brain levels of either 3H-amphetamine or 3H-apomorphine suggests that these behavioral effects were not due to altered peripheral drug metabolism or uptake into the brain. The enhancement of stereotypy produced by EB is viewed as one manifestation of a more complex modulatory influence of estrogen on DA function.

Determination of diffusion and activity coefficients in the gallium-indium system by the contact-melting method

The concentration profile in the liquid layer and the rate of contact melting are derived. These characteristics are found as functions of the self-diffusion coefficients DA and DB of the components and of the activity coefficients in the regular-solution approximation. Comparison of these equations with the experimental concentration profile and with the experimental contact-melting rate allows calculation of DA, DB, and the factork in the expression for Inf in the Ga-In system.