Intrastriatal Administration of Methylmercury Increases In Vivo Dopamine Release

Mercury is a neurotoxin that exists in a number of physical and chemical forms, producing different effects in the brain. In the present work, we have studied the effects of intrastriatal administration of different doses (40 M, 400 M, and 4 mM) of organic mercury (methylmercury, MeHg) on the dopaminergic system of rat striatum, in conscious and freely-moving animals, using microdialysis coupled to Liquid Chromatography. In previous works, we have discussed the effects of chronic and acute administration of MeHg on striatal dopaminergic system assessing changes in both release and metabolism of striatal dopamine (DA). In the present study we report that the intrastriatal administration of different doses of MeHg (40 M, 400 M, and 4 mM) produced significant increases (907 ± 31%, 2324 ± 156%, and 9032 ± 70% of basal levels, respectively for the different doses) in DA release from rat striatal tissue associated with significant decreases in extracellular levels of its main metabolites dihydroxyphenylacetic acid (DOPAC) and homovallinic acid (HVA) using the dose of 4 mM MeHg (35 ± 3% and 48 ± 1%, respectively), whereas non-significant changes in metabolite levels were observed with the doses of 40 M and 400 M MeHg. We explain these effects as a result of stimulated DA release and/or decreased DA intraneuronal degradation.     

Absence of Ret signaling in mice causes progressive and late degeneration of the nigrostriatal system

Support of ageing neurons by endogenous neurotrophic factors such as glial cell line–derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) may determine whether the neurons resist or succumb to neurodegeneration. GDNF has been tested in clinical trials for the treatment of Parkinson disease (PD), a common neurodegenerative disorder characterized by the loss of midbrain dopaminergic (DA) neurons. BDNF modulates nigrostriatal functions and rescues DA neurons in PD animal models. The physiological roles of GDNF and BDNF signaling in the adult nigrostriatal DA system are unknown. We generated mice with regionally selective ablations of the genes encoding the receptors for GDNF (Ret) and BDNF (TrkB). We find that Ret, but not TrkB, ablation causes progressive and adult-onset loss of DA neurons specifically in the substantia nigra pars compacta, degeneration of DA nerve terminals in striatum, and pronounced glial activation. These findings establish Ret as a critical regulator of long-term maintenance of the nigrostriatal DA system and suggest conditional Ret mutants as useful tools for gaining insights into the molecular mechanisms involved in the development of PD.     

Modulation of brain mitochondrial membrane permeability and synaptosomal Ca2+ transport by dopamine oxidation

Effects of dopamine on the membrane permeability transition, thioredoxin reductase activity, production of free radicals and oxidation of sulfhydryl groups in brain mitochondria and the Ca²⁺ uptake by Na⁺-Ca²⁺ exchange and sulfhydryl oxidation in brain synaptosomes were examined. The brain mitochondrial swelling and the fall of transmembrane potential were altered by pretreatment of dopamine in a dose dependent manner. Depressive effect of dopamine on mitochondrial swelling was reversed by 10 g/ml catalase, and 10 mM DMSO. The activities of thioredoxin reductase in intact or disrupted mitochondria were decreased by dopamine (1-100 M), 25 M Zn²⁺ and 50 M Mn²⁺. Dopamine-inhibited enzyme activity was reversed by 10 g/ml SOD and 10 g/ml catalase. Pretreatment of dopamine decreased Ca²⁺ transport in synaptosomes, which was restored by 10 g/ml SOD and 10 mM DMSO. Dopamine (1-100 M) in the medium containing mitochondria produced superoxide anion and hydrogen peroxide, while its effect on nitrite production was very weak. The oxidation of sulfhydryl groups in mitochondria and synaptosomes were enhanced by dopamine with increasing incubation times. Results suggest that dopamine could modulate membrane permeability in mitochondria and calcium transport at nerve terminals, which may be ascribed to the action of free radicals and the loss of reduced sulfhydryl groups.     

Stimulation of ethylene production by catecholamines and phenylethylamine in potato cell suspension cultures

The catecholamines (50 M dopamine, 50 M norepinephrine and 100 M epinephrine) and phenylethylamine (200 M) were found to stimulate ethylene production in potato suspension cultures. When 100 M amino-oxyacetic acid was added together with epinephrine, ethylene release returned to control levels. The endogenous 1-aminocyclopropane-1-carboxylic acid levels were increased in parallel with the release of ethylene, suggesting that the observed effect probably occurs via regulation of aCC synthase. Our results suggest that there is a link between these naturally occurring monoamines and ethylene in plants.Abbreviations AOA amino-oxyacetic acid - ACC 1-aminocyclopropane-1-carboxylic acid - DA dopamine - NE norepinephrine - E epinephrine - CA catecholamines - PEA phenylethylamine     

Dopaminergic Modulation of Neurosecretory Cells in the Crayfish

The main aims of this paper are (a) to locate possible dopaminergic neurons in the eyestalk with anti-tyrosine hydroxylase antibodies, (b) to search for the presence of dopamine (DA) in the nervous structures of the eyestalk, (c) to explore its release, and (d) to test the effect of DA on neurosecretory cells in the eyestalk.Experiments were performed in adult crayfishes Procambarus clarkii, in isolated optic peduncle. Immunocytochemistry was made with the antibody against its precursor synthesizing enzyme tyrosine-hydroxylase. The content and release studies of DA were made using high performance liquid chromatography (HPLC). Extracellular and intracellular recordings were conducted with conventional recording techniques.A large number (2000) of immunopositive somata of different sizes and shapes were identified in various regions of the eyestalk. The majority of somata are of the smallest size (5–25 m diameter). DA content in the eyestalk was 5.6 ± 0.1 pmol per structure; the greatest content is in the MT (over 60%). A basal level release of DA was observed. Incubation of eyestalks in solution containing a high K⁺ concentration increased the DA release (79%). Two effects of DA on the excitability of X-organ neurons were observed; an excitatory effect on neurons of 25 m somata diameter and another inhibitory effect in the group of 35-m somata diameter neurons. The excitation occurs with a depolarization and decrement of membrane conductance in the cell soma while the inhibition occurs with a hyperpolarization and increment of membrane conductance in soma.We concluded the following: (1) Dopamine is present in each optic ganglia of the crayfish eyestalk. (2) There is a basal release of DA from the isolated eyestalk. (3) DA release is enhanced threefold by eyestalk incubation in 40 mM [K⁺] solution. (4) DA selectively excites a population of neurons with low-speed conduction axons, and small somata in the X-organ–sinus gland system, while inhibiting another population characterized by higher axonal conduction speed and large somata. (5) These observations support a role for DA as a neurotransmitter or neuromodulator in the X-organ neurons of the crayfish eyestalk.Dr. Hugo Aréchiga died on September 15th of 2003     

Neuroanatomical,immunocytochemical, and physiological studies of the pharyngeal retractor muscle and its putative regulatory neurons playing a role in withdrawal and feeding in the snail, <Emphasis Type="Italic">Helix pomatia</Emphasis>

We describe the neurons regulating two separate functions of the pharyngeal retractor muscle (PRM), namely sustained contraction during body withdrawal and rhythmic phasic contractions during feeding, in the snail, Helix pomatia. The distribution of central neurons innervating the PRM is organized into two main units; one in the buccal-cerebral ganglion complex, the other in the subesophageal ganglion complex. Serotonin- (5-HT-), FMRFamide- (FMRFa-), and tyrosine-hydroxylase-immunostained neurons are present among the PRM neurons that densely innervate the PRM. 5HT both decreases and increases the amplitude of the electrically evoked contraction between concentrations of 0.1 M and 1 M. Dopamine (DA) only decreases the amplitude of contraction at a 1-M threshold concentration. In contrast, FMRFa increases the amplitude of the contraction and slightly elevates the tone of the PRM but requires a higher threshold (10 M). Assay by high-performance liquid chromatography of 5HT and DA in the PRM has shown that the 5HT level decreases during locomotion but increases during feeding, whereas the DA level increases during locomotion but slightly decreases during feeding. Thus, different segments of the PRM are innervated by neurons from different loci within the central nervous system. The segments of the PRM distal to the pharynx are innervated from loci of the subesophageal ganglion complex suggesting that they mediate withdrawal. The proximal segment of the PRM is innervated from cerebral and buccal loci indicating that these neurons mediate the feeding rhythm produced by buccal and cerebral feeding central pattern generators to induce rhythmic phasic contractions in the PRM during feeding.This work was supported by Hungarian Scientific Research Fund (OTKA) grants (T034106, T037389, T037505), the Wellcome Trust CRIG Programme, and the Wellcome Trust Travel Grant.     

Local Perfusion of Nicotine Differentially Modulates Somatodendritic Dopamine Release in the Rat Ventral Tegmental Area After Nicotine Preexposure

We examined the effects of nicotine perfusion into the ventral tegmental area (VTA) on extracellular dopamine (DA) levels in rats using in vivo microdialysis. Local perfusion with nicotine for 80 min (10–100 M) modestly increased (105–131% of basal) the extracellular DA levels in the VTA of rats that had been pretreated with saline for 5 days. In animals that had been pretreated with nicotine for 5 days (0.3 mg/kg, s.c.), perfusion with nicotine for 80 min (10–100 M) dose-dependently increased the extracellular DA levels in the VTA of rats and did so to a greater extent than in saline-pretreated animals (125–171% of basal). Co-perfusion through the dialysis probe with 100 M mecamylamine, a nonselective nicotinic acetylcholine receptor (nAChR) antagonist, or 100 M dihydro--erythroidine, a high affinity and competitive nAChR antagonist, attenuated the enhancement of extracellular DA levels produced by 100 M nicotine alone. These results suggest that local nicotine challenge potentiated the somatodendritic DA release after nicotine preexposure by stimulation of high-affinity nAChRs in the VTA.     

Histochemical studies on the distribution of catecholamines and 5-hydroxytryptamine after intraventricular injections

Summary Using the histochemical method for the demonstration of DA, NA and 5-HT it has been possible to demonstrate, in reserpine treated rats, that intraventricularly administered DA, NA, -methyl-DA and -methyl-NA in doses of 1–2 g are specifically taken up by the parts of the DA and NA neurons lying close to the ventricles and the subarachnoidal space. The distribution of this uptake is described in detail. No uptake and accumulation of DA and NA was observed unless the monoamineoxidase had been inhibited whereas the -methylated compounds which are resistant to monoamineoxidase accumulated without monoamineoxidase inhibition. Intraventricularly administered 5-HT was specifically taken up and accumulated in the 5-HT neurons within the same zone provided that monoamineoxidase had been inhibited. The distribution of this uptake is described in detail. After high doses of CA (5–10 g) these amines accumulated to some extent also in the 5-HT neurons while no such accumulation was observed in the CA neurons after high doses of 5-HT. Thus, the present results indicate that there exists a specific reserpine-resistant, amine-concentrating mechanism at the nerve cell membrane of CA and 5-HT neurons. In areas where the exogenous amine concentrations probably were high there also occurred an accumulation of DA and NA in the CA neurons although the monoamineoxidase was not inhibited. Finally, in a certain area of the hypothalamus, CA was found to accumulate even after low doses (1–2 g), in nerve cell bodies which probably normally do not contain CA.This study was supported by a research grant from the Swedish Medical Research Council (12x-715-03) and by grants from M. Bergwalls stiftelse and C. Nathorsts stiftelse.     

Immunohistochemical localization of neuropeptide Y in the guinea pig medulla oblongata

Summary The immunohistochemical localization of neuropeptide Y (NPY) was correlated with those of dopamine--hydroxylase (DBH) and vasoactive intestinal polypeptide (VIP) by mapping serial 7 m paraffin sections at three levels of the guina pig lower brainstem: a) area postrema, b) dorsal motor nucleus of the vagus, and c) nucleus prepositus of the hypoglossal nerve. Based on differences in transmitter expression, three populations of NPY-immunoreactive (IR) neurons were distinguished: NPY-IR catecholaminergic cells (NPY/CA), NPY-IR VIP-ergic cells (NPY/VIP), and NPY-IR cells which were not reactive to either DBH or VIP. Within these populations, size differences among neurons in characteristic locations allowed differentiation among the following subpopulations: NPY/CA neurons in the lateral reticular nucleus — magnocellular part (mean neuronal size 538 m²) and parvocellular part (318 m²)-, in the vagus-solitarius complex (433 m²), and in the dorsal strip (348 m²); NPY/VIP neurons in the vagus-solitarius complex (368 m²) and in the nucleus ovalis (236 m²). Apart from scattered NPY-IR cell bodies in the regions listed above, NPY-IR cell bodies in the lateral portion of the nucleus solitarius and in the caudal part of the spinal nucleus of the trigeminal nerve did not exhibit IR to either DBH or VIP. NPY-IR neurons in the area postrema occurred too infrequently for co-localization studies. The differential distribution of heterogeneous NPY-IR cell subpopulations may reflect the involvement of NPY in a variety of neuronal functions.Supported by the Deutsche Forschungsgemeinschaft, grant He 919/6-1     

Activation of BDNF mRNA and protein after seizures in hyperbaric oxygen: implications for sensitization to seizures in re-exposures

Previous studies have demonstrated that exposure to convulsive doses of hyperbaric oxygen (HBO) increases sensitivity to seizures in re-exposures. Because brain derived neurotrophic factor (BDNF) is induced after a variety of seizures and increases cell excitability, it may contribute to the mechanism of sensitization. In this study, a fast induction in BDNF mRNA 2 hr after seizures and a temporary increase in BDNF protein 1 day after seizures induced by 100% O₂ at 5 atm (gauge pressure) were demonstrated in the rat cortex. To determine whether an elevation in BDNF protein level can modify sensitivity to the toxic effect of HBO, recombinant BDNF (12 g) was injected into cerebral ventricles 30 min prior to exposure. Administration of exogenous BDNF significantly shortened latent time to seizures in HBO exposures. We propose that upregulation of BDNF expression in the brain after seizures may contribute to sensitization to HBO toxicity.     

c-Fos Expression by Dopaminergic Receptor Activation in Rat Hippocampal Neurons

While dopamine is likely to modulate hippocampal synaptic plasticity, there has been little information about how dopamine affects synaptic transmission in the hippocampus. The expression of IEGs including c-fos has been associated with late phase LTP in the CA1 region of the hippocampus. The induction of c-fos by dopaminergic receptor activation in the rat hippocampus was investigated by using semiquantitative RT-PCR and immuno-cytochemistry. The hippocampal slices which were not treated with dopamine showed little expression of c-fos mRNA. However, the induction of c-fos mRNA was detected as early as 5 min after dopamine treatment, peaked at 60 min, and remained elevated 5 h after treatment. Temporal profiles of increases in c-fos mRNA by R(+)-SKF-38393 (50 M) and forskolin (50 M) were similar to that of dopamine. An increase in [cAMP] was observed in dopamine-, SKF-, or forskolin-treated hippocampal slices. By immunocytochemical studies, control hippocampal cells showed little expression of c-Fos immunoreactivity. However, when cells were treated with dopamine, an increase in the expression of c-Fos immunoreactivity was observed after treatment for 2 h. The treatment of hippocampal neurons with R(+)-SKF38393 (50 M) or forskolin (50 M) also induced a significant increase in c-Fos expression. These results indicate that the dopamine D1 receptor-mediated cAMP dependant pathway is associated with the expression of c-Fos in the hippocampal neurons. These data are consistent with the possible role of endogenous dopamine on synaptic plasticity via the regulation of gene expression. Furthermore, these results imply that dopamine might control the process of memory storage in the hippocampus through gene expression.     

Changes in extracellular levels of glutamate and aspartate in rat substantia nigra induced by dopamine receptor ligands: In vivo microdialysis studies

The microdialysis technique was utilized to study the local effects of D₁ and D₂ family type dopamine (DA) receptor (R) ligands on the in vivo release of endogenous glutamate (GLU) and aspartate (ASP) from rat substantia nigra (SN). Addition to the dialysis perfusion solution of either D₁-R and D₂-R agonists, such as SKF-38393 (50 and 100 M) and Quinpirole (5 and 10 M), resulted in dose-dependent increases in extracellular concentrations of GLU and ASP, respectively. The SKF-38393 and Quinpirole-induced effects were reduced by SCH-23390 (0.5 M), a D₁-R antagonist, and by Spiperone (1.0 M), a D₂-R antagonist, respectively. However, SCH-23390 and Spiperone did increase GLU and ASP extracellular concentrations. Local infusion with Tetrodotoxin (TTX) (1.0 M), a blocker of voltage-dependent Na⁺ channels, increased basal extracellular levels of GLU. In addition, co-infusion of TTX and SKF-38393 evoked increases in extracellular GLU levels higher than those observed after SKF-38393 alone. Finally, chemical lesions of nigral DA cells with 6-OH-DA increased the basal extracellular levels of GLU. It is proposed that the release of GLU and ASP from SN may be regulated by D₁- and D₂-receptors present in this basal ganglia structure. In addition, part of the D₁ receptors present in SN might be located presynaptically on GLU-containing nerve endings.     

Endogenous phosphorylation of rat brain synaptosomal plasma membranes in vitro: Some methodological aspects

The time course of endogenous phosphorylation in vitro of total or separted synaptic plasma membrane proteins (SPM) has been correlated with that of hydrolysis of the phosphate donor (ATP) in the incubation medium. The ATP/SPM ratio in the medium was varied. In a low-ratio medium (7.5 M ATP; 2.2 g SPM/l) a complete hydrolysis of ATP occurred almost instantaneously as was measured by the release of free phosphate in and the disappearance of ATP from the medium. As a consequence, only a very short peak of phosphorylation, followed by dephosphorylation was observed. However, when higher ATP/SPM ratios were used (200 M ATP; 0.4 g SPM/l and 500 M ATP; 0.4 g SPM/l), the incorporation of phosphate into SPM proteins was linear for 20 sec, and the maximum level of phosphate incorporation was increased. Similar results were obtained after separation of³²P-labeled phosphoproteins by slab gel electrophoresis. However, analysis of the autoradiographs obtained fromone SPM preparation under different ATP/SPM ratios revealed dependence of phosphorylation of individual protein bands on the conditions used.     

Effect of transferrin on amphibian limb regeneration: a blastema cell culture study

Summary In order to study mitogenic control during axolotl limb regeneration, we have developed a primary blastema cell culture as a very sensitive bioassay for blastema mitogens. Transferrin, an iron-binding glycoprotein which has been shown to be the neurotrophic factor for muscle cells, is the mitogen which has been analysed in the present report. Addition of approximately 2 g human transferrin/ ml of serum-free culture medium enhances blastema cell proliferation 11-fold over control levels and 2-fold over that produced by the addition of nerve extracts or purified growth factors extracted from nerve tissues (basic and acidic fetal growth factor, FGF). At a higher concentration (20 g/ml), transferrin alone has no mitogenic effect unless the medium is also supplemented with FeCl₃ (100 M). The results are discussed with regard to the sensitivity of the blastema cell culture bioassay and in the context of the neurotrophic theory of urodele limb regeneration.     

Destruction of Midbrain Dopaminergic Neurons by Using Immunotoxin to Dopamine Transporter

1. The ability to target specific neurons can be used to produce selective neural lesions and potentially to deliver therapeutically useful moieties for treatment of disease. In the present study, we sought to determine if a monoclonal antibody to the dopamine transporter (anti-DAT) could be used to target midbrain dopaminergic neurons.2. The monoclonal antibody recognizes the second, large extracellular loop of DAT. The antibody was conjugated to the ribosome-inactivating protein saporin, and stereotactically pressure microinjected into either the center of the striatum or the left lateral ventricle of adult, male Sprague-Dawley rats.3. Local intrastriatal injections produced destruction of dopaminergic neurons in the ipsilateral substantia nigra consistent with suicide transport of the immunotoxin. Intraventricular injections (i.c.v.) produced significant loss of dopaminergic neurons in the substantia nigra and ventral tegmental area bilaterally without evident damage to any other aminergic structures such as the locus coeruleus and raphé nuclei. To confirm the anatomic findings, binding of [³H]mazindol to DAT in the striatum and midbrain was assessed using densitometric analysis of autoradiograms. Anti-DAT-saporin injected i.c.v. at a dose of 21 g, but not 8 g, produced highly significant decreases in mazindol binding consistent with loss of the dopaminergic neurons.4. These results show that anti-DAT can be used to target midbrain dopaminergic neurons and that anti-DAT-saporin may be useful for producing a lesion very similar to the naturally occurring neural degeneration seen in Parkinson's disease. Anti-DAT-saporin joins the growing list of neural lesioning agents based on targeted cytotoxins.     

The endogenous development of four new species of Isospora Schneider, 1881 (Apicomplexa: Eimeriidae) from Australian geckos

Four new species of Isospora are described from Australian geckoes. Isospora gehyrae n. sp. from Gehyra cf. variegata in South Australia have 18.5-22.5×17.5–20.0 m oöcysts with 10.0-12.5×7.5-9.0 m sporocysts; endogenous stages develop in the host cell cytoplasm. Of the two species found in Heteronotia binoei from northern Queensland, Isospora cytoheteronotis n. sp., with oöcysts of 20.0-26.0×17.5-25.0 m and sporocysts of 10.0-13.5×7.5-11.5 m, undergoes endogenous development in its host cell cytoplasm, whereas I. nucleoheteronotis n. sp., with oöcysts of 17.5-22.5×17.5-21.5 m and sporocysts of 9.0-12.5×6.5-10.0 m, develops in the host cell nucleus. I. oedurae n. sp. from Oedura rhombifer in northern Queensland has oöcysts of 22.5-25.0×22.5-24.0 m and sporocysts of 12.5-14.0×7.5-11.5 m, and undergoes endogenous development in its host cell nuclei.     

Reciprocal Innervation between Serotonergic and GABAergic Neurons in Raphe Nuclei of the Rat

Midbrain slices containing the dorsal and medial raphe nuclei were prepared from rat brain in order to study serotonergic-GABAergic interaction. The slices were loaded with either [³H] serotonin or [³H]GABA, superfused and the electrically induced efflux of radioactivity was determined. The GABA_A receptor agonist muscimol (3 to 30 M) and the GABA_B receptor agonist baclofen (30 and 100 M) inhibited [³H]serotonin and [³H]GABA release. These effects of muscimol were reversed by the GABA_A antagonists bicuculline (100 M). The GABA_B antagonist phaclofen (100 M) also antagonized the baclofen-induced inhibition of [³H]serotonin and [³H]GABA release. Phaclofen by itself increased [³H]serotonin release but it did not alter [³H]GABA overflow. Muscimol (10 M) and baclofen (100 M) also inhibited [³H]serotonin release after depletion of GABAergic neurons by isoniazid pretreatment. These findings indicate the presence of postsynaptic GABA_A and GABA_B receptors located on serotonergic neurons. The 5-HT_1A receptor agonist 8-OH-DPAT (0.01 to 1 M) and the 5-HT_1B receptor agonist CGS-12066A (0.01 to 1 M) inhibited the electrically stimulated [³H]serotonin and [³H]GABA release. The 5-HT_1A antagonist WAY-100135 (1 M) was without effect on [³H]serotonin and [³H]GABA efflux by itself but it reversed the 8-OH-DPAT-induced transmitter release inhibition. During KCl (22 mM)-induced depolarization, tetrodotoxin (1 M) did not alter the inhibitory effect of CGS-12066A (1 M) on [³H]GABA release, it did blocked, however, the ability of 8-OH-DPAT (1 M) to reduce [³H]GABA efflux. After depletion of raphe serotonin neurons by p-chlorophenylalanine pretreatment, CGS-12066A (1 M) still inhibited [³H]GABA release whereas in serotonin-depleted slices, 8-OH-DPAT (1 M) was without effect on the release. We conclude that reciprocal influence exists between serotonergic projection neurons and the GABAergic interneurons or afferents in the raphe nuclei and these interactions may be mediated by 5-HT_1A/B and GABA_A/B receptors. Both synaptic and non-synaptic neurotransmission may be operative in the 5-HTergic-GABAergic reciprocal interaction which may serve as a local tuning in the neural connection between cerebral cortex and midbrain raphe nuclei.     

Influence of sarmesin on some dopamine-related types of behaviour

Summary The present study was undertaken to investigate the effects of sarmesin, an analogue of [Sar¹] angiotensin II (ANG II) where the tyrosine hydroxyl group in position 4 is methylated, on dopamine (DA)-related paradigms: locomotor and exploratory behaviour as well as apomorphine (3 mg/kg, ip)-induced stereotypy in rats. Sarmesin (0.5 and 1 g, icv) significantly decreased ambulation and rearing movements, and blocked the inhibitory effect of ANG II (0.1 g) on both types of activity. Sarmesin induced biphasic effects on apomorphine-induced stereotypy depending on the dose increase (0.5 and 5 g, icv) and decrease (10 g). Moreover, sarmesin (5 g) blocked the inhibitory effect of ANG II (2 g, icv) on apomorphine stereotypy. Taken together, these results suggest that sarmesin might interact with AT₁ and AT₂ receptor subtypes. The results further confirm the statement for ANG II-DA interaction in brain structures involved in these types of behaviour.     

Characteristics of the ATP-ase activity of isolated neurons of rabbit

Summary Isolated and homogenised Deiters' neurons from the lateral vestibular nucleus of rabbit in a Krebs-Ringer solution containing no added Mg⁺⁺, 1.3 moles/ ml and 5 moles/ml Mg⁺⁺, broke down ATP at the maximal rate of 0.29+-0.20, 2.40+–0.20, and 5.95+–0.63 moles/cell/hr. In 1.3 mM Mg⁺⁺ solution the single cell homogenates took up phosphate at the mean rate of 2.6+–0.2 moles/cell/hr. If the rabbits were injected 1 hour before with 20 mg/kg body weight of 2-amino-1-propene-1,1,3, tricarbonitrile (triap), the breakdown of ATP in these latter media was 0.82+–0.44, 2,5+–0.60, and 6.7+– 1.1 moles/cell/hr, respectively, and the quantity of inorganic liberated did not decrease.     

Mechanisms Underlying Domoic Acid–Induced Dopamine Release from Striatum: An in Vivo Microdialysis Study

The brain microdialysis technique has been used to examine the in vivo effects of the neurotoxin domoic acid (an ionotropic glutamate receptor agonist) on dopamine (DA) release in the striatum of conscious and freely moving rats. Local application of domoic acid (500M) through the microdialysis probe produced an increase in striatal DA content (597±96% with respect to basal levels). The release of DA induced by domoic acid was not attenuated in a Ca⁺²-free medium (469±59%) or after pretreatment with 10mg/kg reserpine (533±79%). Intrastriatal infusion of 1M tetrodotoxin (TTX) partially reduced the domoic acid–evoked DA release (278±34%). Moreover, domoic acid perfusion had no effect on K⁺-evoked DA release. The results suggest that domoic acid increases the striatal DA release according to a reserpine-independent, calcium-independent and partially TTX-insensitive mechanism, suggesting that these effects probably involve a nonexocytotic process. On the other hand, the inhibitor of DA uptake nomifensine (10M) reduced the domoic acid–evoked DA release (356±59%), suggesting that a carrier-dependent mechanism could be involved in the effect of domoic acid on the striatal DA levels.