5-HT(1B) receptor-mediated regulation of serotonin clearance in rat hippocampus in vivo.

The 5-hydroxytryptamine (5-HT; serotonin) transporter (5-HTT) is important in terminating serotonergic neurotransmission and is a primary target for many psychotherapeutic drugs. Study of the regulation of 5-HTT activity is therefore important in understanding the control of serotonergic neurotransmission. Using high-speed chronoamperometry, we have demonstrated that local application of 5-HT(1B) antagonists into the CA3 region of the hippocampus prolongs the clearance of 5-HT from extracellular fluid (ECF).

Long-term infusion of nonphysiologic solutions into brain parenchyma: effects of pH, osmolarity, and flow rate.

The effects of long-term (3-day) infusion of nonphysiologic solutions into brain parenchyma were investigated in male Fischer (F344) 344 rats. Two weeks prior to infusion, a guide cannula was placed into the striatum, substantia nigra, or hippocampus. Solutions were infused continually for 3 days at flow rates of 0.

Dopaminergic therapy improves upper limb motor performance in aged rhesus monkeys.

The potential of dopaminergic treatments to improve upper limb motor movements was tested in 7 aged rhesus monkeys using L-3,4-dihydroxyphenylalanine (L-dopa) or the selective dopamine uptake inhibitor 1-2(bis[4-fluorophenyl] methoxy]ethyl)-4-(3-phenylpropyl) piperazine hydrochloride (GBR-12909). Six young monkeys were studied for comparison. L-Dopa or GBR-12909 improved upper limb motor performance by up to 40% in the aged animals.

In vivo microdialysis studies of age-related alterations in potassium-evoked overflow of dopamine in the dorsal striatum of Fischer 344 rats.

Intracerebral microdialysis was used to measure basal levels and potassium (K(+))-stimulated overflow of dopamine (DA), homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC), in the dorsal striatum of young (6 months) and aged (24 months) Fischer 344 (F344) rats. Basal levels of HVA were lower in aged rats whereas basal DA and DOPAC did not differ significantly between the two groups. The administration of three low to moderate doses of K(+) (10, 25, and 50 mM) through the microdialysis probe for one collection period revealed differences between the two age groups of F344 rats.

Glial cell line-derived neurotrophic factor is essential for postnatal survival of midbrain dopamine neurons.

Glial cell line-derived neurotrophic factor (GDNF) is one of the most potent trophic factors that have been identified for midbrain dopamine (DA) neurons. Null mutations for trophic factor genes have been used frequently for studies of the role of these important proteins in brain development. One problem with these studies has been that often only prenatal development can be studied because many of the knockout strains, such as those with GDNF null mutations, will die shortly after birth.

Adsorption-based electrochemical detection of nonelectrochemically active analytes for capillary electrophoresis.

A sensitive electrochemical detection method (ECD) for capillary electrophoresis has been developed that is applicable to a much wider range of analytes than more conventional ECD methods. Using a modified Osteryoung square-wave voltammetry method, the adsorption of what are normally considered nonelectrochemically active analytes onto a platinum electrode was found to produce a concentration-proportional response. Although the mechanisms that cause this response may be complex, it appears that it is due to changes in the electrode/solution interface that accompany adsorption of the analyte onto the electrode rather than a simple redox process.

Functional MRI of apomorphine activation of the basal ganglia in awake rhesus monkeys.

Functional magnetic resonance imaging (fMRI) was used to analyze blood oxygen level-dependent (BOLD) responses in the nigrostriatal system (caudate nucleus, putamen and substantia nigra) of awake rhesus monkeys to systemic apomorphine administration. The study (1) measured BOLD responses as an index of neuronal activity in the three structures following injections of the mixed D1/D2 agonist, and (2) assessed the effects of isoflurane anesthesia on the fMRI responses. Compared to control saline injections, 0.

Silicate polymerization for the preparation of bed-retention frits in capillary electrochromatography.

Bubble formation, which is associated with bed-retention frits, is a critical experimental problem in capillary electrochromatography systems. In this investigation, porous silica frits were prepared via spot-heating of a silicate solution, and the effects of several experimental parameters on their performance were studied. The optimal sodium silicate concentrations were 10.

Ceramic-based multisite microelectrodes for electrochemical recordings.

This paper describes the development and characterization of ceramic-based multisite arrays for electrochemical recordings in biological systems. These electrodes represent a parallel technology to the design of microelectrodes using silicon substrates. The ceramic substrates are stronger than silicon and are nonconducting, which makes them better suited for in vivo electrochemical measurements.

Effects of chronic antidepressant treatments on serotonin transporter function, density, and mRNA level.

To investigate functional changes in the brain serotonin transporter (SERT) after chronic antidepressant treatment, several techniques were used to assess SERT activity, density, or its mRNA content. Rats were treated by osmotic minipump for 21 d with the selective serotonin reuptake inhibitors (SSRIs) paroxetine or sertraline, the selective norepinephrine reuptake inhibitor desipramine (DMI), or the monoamine oxidase inhibitor phenelzine. High-speed in vivo electrochemical recordings were used to assess the ability of the SSRI fluvoxamine to modulate the clearance of locally applied serotonin in the CA3 region of hippocampus in drug- or vehicle-treated rats.

Critical decline in fine motor hand movements in human aging.

Background: Slowing of motor movements in human aging is a well-known occurrence, but its biologic basis is poorly understood. Reliable quantitation may refine observations of this phenomenon to better aid research on this entity.

Methods: A panel equipped with timing sensors under computer control was used to measure upper extremity movement times in two groups of healthy individuals: adults younger than 60 years of age (n = 56; range, 18-58 years) and adults older than 60 years of age (n = 38; range, 61-94 years).

Capillary electrophoresis with end-capillary potentiometric detection using a copper electrode.

Potentiometric end-capillary detection in capillary electrophoresis has the advantage of relatively easy miniaturisation without having to compromise the concentration sensitivity. Potentiometric end-capillary detection using a copper electrode is also attractive because of the sensitive detection of many inorganic and organic UV-transparent ions and the ability to work in both direct and indirect mode. In this work, detection of a number of common anions in a tartrate electrolyte at pH 3 was studied.

An automated movement assessment panel for upper limb motor functions in rhesus monkeys and humans.

As part of our studies of age-associated changes in motor functions, we have designed an automated movement assessment panel (MAP) to evaluate upper limb and hand movements. Here we describe two versions of the MAP, one for human testing and one for nonhuman primates, and methods for conducting parallel tests in rhesus monkeys and human volunteers. The results are reported from a battery of tests on young adult rhesus monkeys (n = 10, 5-8 years old), young adult human subjects (n = 10, 18-22 years old) and ten aged human subjects (n = 10, 66-68 years old) to demonstrate the capability of the MAP in quantifying arm and hand movement times.

5-HT1B antagonists modulate clearance of extracellular serotonin in rat hippocampus.

In vivo chronoamperometry was used to determine the effects of locally applied antagonists of the serotonin-1B (5-HT1B) receptor (cyanopindolol, 5-HT-moduline and methiothepin) on the clearance of 5-HT in the CA3 region of the dorsal hippocampus and the corpus callosum (a brain region devoid of serotonin transporters and 5-HT1B receptors) of the rat. When 5-HT was pressure ejected into these regions, reproducible signals were detected. In the CA3 region, local application of 5-HT1B antagonists decreased the rate of clearance of the serotonin signal comparably to the selective 5-HT uptake inhibitor (SSRI), fluvoxamine.

Capillary electrophoresis of some tetracycline antibiotics coupled with reductive fast cyclic voltammetric detection.

The separation and quantitative performance parameters for tetracycline, chlortetracycline and oxytetracycline antibiotics were investigated by capillary zone electrophoresis coupled with fast cyclic voltammetric detection. Optimization of pH and complexation with a boric acid-sodium tetraborate buffer provided good resolution of all compounds. Detection by electrochemical reduction using fast on-line cyclic voltammetric detection with a Hg-film-microm electrode gave detection limits (2 x peak-to-peak baseline noise) of 7 x 10(-7) mol/l for tetracycline and chlortetracycline, and 1.

Multiple single-unit recordings in the striatum of freely moving animals: effects of apomorphine and D-amphetamine in normal and unilateral 6-hydroxydopamine-lesioned rats.

Ensembles of striatal neurons were recorded in freely moving normal and unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats using chronically implanted electrode arrays. Animals received bilateral striatal implants of two 16-microwire arrays 1 week before recordings. Identified striatal neurons were categorized as medium spiny-like and large aspiny-like based on a combination of their activity autocorrelations and firing rates.

Multiple single units and population responses during inhibitory gating of hippocampal auditory response in freely-moving rats.

Paired clicks were presented to awake, freely-moving rats to examine neuronal activity associated with inhibitory gating of responses to repeated auditory stimuli. The rats had bundles of eight microwires implanted into each of four different brain areas: CA3 region of the hippocampus, medial septal nucleus, brainstem reticular nucleus, and the auditory cortex. Single-unit recordings from each wire were made while the local auditory-evoked potential was also recorded.

Differences in pharmacological properties of dopamine release between the substantia nigra and striatum: an in vivo electrochemical study.

The properties of dopamine (DA) release in the rat substantia nigra (SN) and striatum were investigated using high-speed chronoamperometric recordings in brain slices. In both brain regions, a 2-min bath superfusion with 30 mM KCl produced robust DA-like electrochemical signals, with the mean amplitude of the signal being >10-fold greater in the striatum than the SN. The reproducibility of the response was confirmed by a second stimulus (S2)/first-stimulus (S1) ratio of >0.

In vivo dopamine clearance rate in rat striatum: regulation by extracellular dopamine concentration and dopamine transporter inhibitors.

Dopamine transporter (DAT) inhibitors are expected to decrease dopamine (DA) clearance from the extracellular space of the brain. However, mazindol and cocaine have been reported to "anomalously" increase DA clearance rate. To better understand in vivo DAT activity both in the absence and presence of DAT inhibitors, clearance of exogenously applied DA was measured in dorsal striata of urethane-anesthetized rats using high-speed chronoamperometry.

Methodology for coupling local application of dopamine and other chemicals with rapid in vivo electrochemical recordings in freely-moving rats.

Methodology is presented for constructing and using an electrode/microcannulae assembly that allows in vivo electrochemical measurements coupled with local application of dopamine (DA) and other chemicals in the unanesthetized freely-moving rat. Rats were implanted with a voltammetric electrode constructed of a carbon fiber sealed in fused silica tubing attached to a pair of stainless steel guide cannulae, into which fused silica injection cannulae were inserted for local application of DA and other chemicals. Precise delivery of nanoliter volumes was accomplished using a syringe drive combined with a fluid swivel to deliver the solutions to the injection cannulae.

Age-related reductions in [3H]WIN 35,428 binding to the dopamine transporter in nigrostriatal and mesolimbic brain regions of the fischer 344 rat.

In the present study, we used the potent cocaine analog [3H]WIN 35, 428 to map and quantify binding to the dopamine transporter (DAT) within the dorsal striatum, nucleus accumbens, substantia nigra, and ventral tegmental area in young (6-month-old), middle-aged (12-month-old), and aged (18- and 24-month-old) Fischer 344 rats. Quantitative autoradiographic analysis of indirect [3H]WIN 35,428 saturation curves revealed two-site binding for all four brain regions in every age group. The percentage of binding to the high- or low-affinity sites did not differ with age or region and was approximately 50%.

Voltage-dependency of the dopamine transporter in the rat substantia nigra.

The possible voltage-dependence of the dopamine transporter (DAT) was investigated using electrophysiological and electrochemical recordings in rat brain slices containing the substantia nigra (SN). Whole-cell patch clamp recordings of DA neurons, revealed that addition of 15 mM KCl rapidly depolarized the membrane potential by approximately 20 mV, whereas these cells were hyperpolarized approximately 10 mV by DA (10 microM) and approximately 14 mV by the GABAB-receptor agonist baclofen (30 microM). High-speed chronoamperometric recordings were used to monitor clearance properties of exogenously applied DA signals during similar manipulations.

Age-related changes in the capacity, rate, and modulation of dopamine uptake within the striatum and nucleus accumbens of Fischer 344 rats: an in vivo electrochemical study.

Age-related changes in the capacity, rate, and modulation of dopamine (DA) uptake within the striatum and the nucleus accumbens core of Fischer 344 rats were investigated using in vivo electrochemical recordings coupled with local drug application techniques. Equimolar amounts of DA were pressure ejected into the striatum and the nucleus accumbens of 6-, 12-, 18-, and 24-month old rats. The DA ejections produced larger DA signal amplitudes in the older rats, suggesting age-related differences in the capacity to clear extracellular DA.

Auditory P50 in schizophrenics on clozapine: improved gating parallels clinical improvement and changes in plasma 3-methoxy-4-hydroxyphenylglycol.

Schizophrenic patients have decreased inhibition of the P50 auditory evoked potential response to the second of two paired click stimuli delivered 500 ms apart. This deficit in inhibitory gating does not change during treatment with typical neuroleptics. We recently reported that neuroleptic-resistant schizophrenics had enhanced P50 gating after 1 month of clozapine treatment, if they responded with decreased clinical symptoms.

GDNF improves dopamine function in the substantia nigra but not the putamen of unilateral MPTP-lesioned rhesus monkeys.

Microdialysis measurements of dopamine (DA) and DA metabolites were carried out in the putamen and substantia nigra of unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned rhesus monkeys that received intraventricular injections of vehicle or glial-derived neurotrophic factor (GDNF, 300 microg) 3 weeks prior to the microdialysis studies. Following behavioral measures in the MPTP-lesioned monkeys, they were anesthetized with isoflurane and placed in a stereotaxic apparatus. Magnetic resonance imaging (MRI)-guided sterile stereotaxic procedures were used for implantations of the microdialysis probes.