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D B Neill

Publications and source records attributed to D B Neill.

At least 37 records · Page 2Linked to original sources

Striatal dopamine activity and unilateral barpressing in rats.

A micro-punch tissue assay was used to measure changes in dopamine content at twenty-six sites within the striatum of rats trained to barpress exclusively with one forepaw for food pellets. Analysis of dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), was carried out using HPLC with electrochemical detection. The barpress group had a significantly higher DOPAC/DA ratio in both the contralateral and ipsilateral hemispheres when compared to feeding and homecage controls. The DOPAC/DA ratio is considered to be a measure of dopaminergic neuronal activity, thus suggesting a bilateral activation of the neostriatal dopaminergic afferents as a result of the motor performance. Topographical analysis within the barpress group revealed an anterior-posterior, medial-lateral gradient of dopaminergic activity with the posterior and lateral sites showing the greatest increases over the controls. The results of this experiment indicate that localized changes in neuronal activity can be monitored with the micro-punch assay-HPLC/EC technique and that voluntary motor behavior produces an activation of the striatal dopamine system.

3,4-Dihydroxyphenylacetic Acid↗

Dopamine depletion in a striatal subregion disrupts performance of a skilled motor task in the rat.

Unilateral 6-hydroxydopamine injections into the lateral neostriatum disrupted the ability of rats to retrieve small food pellets with the contralateral forepaw. Similar injections into the medial striatum did not interfere with performance accuracy. Dopamine assays indicated that of the 5 striatal subregions analyzed, the lateral striatum at the level of the anterior commissure was most directly related to the behavioral deficit. The behavioral results are interpreted as providing evidence in support of a sensory role for the lateral striatal dopamine system.

Animals↗

In vivo voltammetric determination of the kinetics of dopamine metabolism in the rat.

In vivo voltammetry at carbon paste electrodes placed in the striatum of chloral hydrate-anesthetized rats was used to monitor changes in extracellular 3,4-dihydroxyphenylacetic acid (DOPAC) following 1-min periods of electrical stimulation of the ascending nigro-striatal pathways. Statistical analysis of resultant changes in DOPAC allows simultaneous determination of the rate constants for the turnover of both dopamine (DA) (0.046/min) and DOPAC (0.053/min.). The data demonstrate that there are substantial temporal differences between neuronal release of DA and changes in striatal DOPAC levels. This should be considered when metabolite measurements are used as an index of neurotransmitter activity.

3,4-Dihydroxyphenylacetic Acid↗

Neuroleptics increase striatal catecholamine metabolites but not ascorbic acid in dialyzed perfusate.

To determine the effects of dopamine receptor blockade upon oxidizable components of striatal extracellular fluid, high-performance liquid chromatography (HPLC) with electrochemical detection was used to assay levels of ascorbic acid, dihydroxyphenylacetic acid (DOPAC) homovanillic acid (HVA), and 5-hydroxyindole acetic acid (5-HIAA) in perfusates obtained from unanesthetized rats following i.p. administration of haloperiodol (1.0 mg/kg) or clozapine (20 mg/kg). Striatal push-pull perfusion was performed by passing artificial CSF between two pulled glass micropipets, encapsulated by a hollow, semipermeable cellulose fiber, thereby limiting recovery to compounds under mw 5000. Samples were directly injected into a C-18 column at half-hour intervals before and after neuroleptic administration. Haloperidol administration resulted in increases in extracellular DOPAC and HVA while failing to alter 5-HIAA or ascorbic acid levels. Similar results were found with clozapine, except for a more variable individual response to the drug; clozapine also produced a small increase in 5-HIAA levels. Animals given a saline injection did not show increases in any of these compounds. These data confirm the involvement of extracellular dopamine metabolites in the electrochemical signal increases observed in vivo following dopamine receptor blockade and provide evidence that extracellular ascorbic acid in the striatum is insensitive to peripheral neuroleptic administration.

3,4-Dihydroxyphenylacetic Acid↗

Extracellular ascorbic acid increases in striatum following systemic amphetamine.

Push-pull perfusion of the anterior striatum was performed in freely moving rats which were administered 4 mg/kg d-amphetamine sulfate. Ascorbic acid was measured in the perfusate using high performance liquid chromatography with electrochemical detection. Increased extracellular ascorbic acid resulted from the amphetamine, lasting over a period of two hours. The time course of the increase corresponded to the increased oxidation current measured by intrastriatal chonoamperometry under equivalent conditions.

Animals↗

Behavioral observation and intracerebral electrochemical recording following administration of amphetamine in rats.

Intracerebral electrochemistry (chronoamperometry) was performed on rats that were administered 1, 4, and 8 mg/kg doses of amphetamine. Graphpoxy working electrodes were implanted bilaterally in nucleus accumbens (ACC) and ventral anterior stratum (VAS). Following drug injection, locomotor and stereotyped behaviors were observed. Intracerebral electrochemical signals reliably increased following injection of amphetamine. The magnitude of these increases did not change significantly across the dose range tested for VAS electrodes. ACC electrodes had increases similar in magnitude to VAS electrodes at 1 and 4 mg/kg. At 8 mg/kg increases obtained from ACC electrodes were significantly lower than those recorded from VAS. Onset of the change in electrochemical signal paralleled the onset of activity or stereotypy but the subsequent declines in signal and behavior were only loosely correlated. At the 4 mg/kg dose, the magnitude of signal increase from striatum was negatively correlated with indices of stereotypy and positively correlated with locomotor counts.

Amphetamine↗

Gas chromatographic-mass spectrometric determination of glutamic acid decarboxylase activity in subregions of rat brain.

A quantitative gas chromatographic--mass spectrometric method has been developed for the determination of glutamic acid decarboxylase (GAD) activity in subregions of rat brain. The five subregions analyzed, weighing approximately 2.51 mg each, were globus pallidus, entopeduncular nucleus, ventromedial thalamus, and substantia nigra medical and lateral. The activity of the GAD enzyme has been determined indirectly by measurement of gamma-aminobutyric acid (GABA) using gamma-[2,2-2H2] aminobutyric acid as the internal standard. Both compounds were quantitatively converted to trimethylsilyl-GABA and trimethylsilyl-[2H2]GABA in 90 min with hexamethylchlorosilane, trimethylchlorosilane, pyridine and N,O-bis(trimethylsilyl)trifluoroacetamide silylating agents. Using selective ion monitoring and electron impact ionization at 70 eV, the limit of detection was 15 ng GABA per mg tissue. This method is compared with a fluorimetric procedure.

Animals↗

Determination of dopamine, homovanillic acid and 3,4-dihydroxyphenylacetic acid in rat brain striatum by high-performance liquid chromatography with electrochemical detection.

Two procedures using liquid chromatography with electrochemical detection are described for the determination of dopamine (DA) and its two acidic metabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), in subregions of rat striatum and nucleus accumbens. A strong cation-exchange column was used for DA analysis and a C18 reversed-phase column was used for the analysis of the metabolites. Effects of pH, temperature and percentage of methanol on the retention time of HVA and DOPAC were studied. Levels of these compounds in the subregions of rat stratum and nucleus accumbens are reported.

3,4-Dihydroxyphenylacetic Acid↗

Gas chromatographic-mass spectrometric determination of dopamine in subregions of rat brain.

A quantitative gas chromatographic-mass spectrometric assay was developed for the determination of dopamine in subregions of rat brain. Five tissue punches weighing approximately 1.7 mg each were taken from the nucleus accumbens and four neostriatal regions differing in anterior-posterior level. The dopamine extracted from the tissue was treated with pentafluoropropionic anhydride (PFP) and quantitatively formed dopamine-(PFP)3. The derivatizing procedure took 15 min and the retention time for dopamine-(PFP)3 and its deuterated analogue [1,1,2,2-2H4]dopamine-(PFP)3) was 120 sec. Selective ion monitoring was utilized to monitor the gas chromatographic effluent. Ions were generated by electron impact ionization. The assay was able to measure concentrations of 1 nanogram dopamine per milligram protein. An anterior-posterior gradient of dopamine was observed in the striatum. This assay should be useful in studies examining the effects of experimental manipulations on dopamine content in relatively small areas of brain tissue.

Animals↗

An automated electrochemical method for in vivo monitoring of catecholamine release.

A computer-controlled electrochemical system for the in vivo monitoring of catecholamines and their metabolites is described. The system is composed of a microcomputer, real time interface board, and a commercial electrochemical instrument. The method and theory of the electrochemical technique are explained and details concerning the construction of the electrodes are given. Descriptions of the hardware and software are also provided. Experimental results are presented to demonstrate the use of the system for long-term in vivo monitoring and for detecting the change in the level of oxidizable species after amphetamine administration.

Animals↗

Identification of a subregion within rat neostriatum for the dopaminergic modulation of lateral hypothalamic self-stimulation.

Experiments were conducted to test the hypothesis that the involvement of neostriatal dopaminergic transmission in lateral hypothalamic self-stimulation might be specific to a striatal subregion. Crystalline application of dopamine or D-amphetamine increased self-stimulation rate only when made to ventral anterior striatum (VAS); more dorsal or posterior applications were ineffective. A comparison of dose-response functions for dopamine using solution injections in VAS and posterior striatum (PS) confirmed that only VAS was responsive. Injections or applications of 6-hydroxydopamine suppressed responding only when made into VAS. Haloperidol injections decreased responding only for VAS and not PS injection sites. Applications or injections of scopolamine often increased responding when made into VAS, but this effect was unreliable. Applications or injections of scopolamine to more posterior sites consistently suppressed responding. It was concluded that dopaminergic transmission in VAS, alone among the striatal sites tested, is facilitatory on hypothalamic self-stimulation. The effects of drug applications to nucleus accumbens were generally similar to VAS, and it was suggested that these areas may be functionally similar. An examination of the known afferents to VAS indicated that this area of neostriatum, like n. accumbens, may be influenced by activity in limbic structures. This anatomy may help provide an understanding of how neostriatum, traditionally considered to have a motor function, might be involved in central reward processes.

Animals↗

Anatomical specificity within rat striatum for the dopaminergic modulation of DRL responding and activity.

The direct application of microgram quantities of crystalline dopamine, D-amphetamine, or scopolamine to the ventral anterior region of the neostriatum of rats decreased response efficiency on a 'differential reinforcement of low rate' 10 sec schedule of reinforcement. Similar applications to the dorsal globus pallidus or posterior striatum either did not alter or increased response efficiency. A comparison of dose-response functions for injections of dopamine in solution into ventral anterior, central and posterior striatum confirmed that only injections into ventral anterior striatum (VAS) decreased response efficiency on the DRL schedule. The same striatal map was found for the dopamine-induced increase in spontaneous locomotor activity in tilt boxes. It was concluded that dopaminergic transmission in ventral anterior striatum, in contrast to the other striatal and pallidal sites tested, is involved in the modulation of behavioral arousal.

Animals↗

Deficits in behavioral responding to regulatory challenges after lesions of ventrobasal thalamus in rats.

Electrolytic lesions of the posteromedial portion of the ventrobasal thalamic complex of rats impaired the feeding response to glucoprivation produced by systemic injection of 2-deoxy-D-glucose and the sodium appetite induced by injections of desoxycorticosterone, and produced abnormally low water intake in the absence of food. Drinking elicited by intracellular dehydration was not consistently affected. Lesions of the ventral anterior nucleus of the thalamus only impaired the feeding response to glucoprivation. The behavioral changes observed after posterior ventrobasal thalamic damage may be related to a disruption of gustatory, visceral, and somatosensory thalamic connections with the corpus striatum and neocortex.

Animals↗

Frontal-striatal control of behavioral inhibition in the rat.

The direct application of crystalline dopamine, D-amphetamine or scopolamine in microgram quantities to the ventral anterior region of the corpus striatum (VAS) of rats increased their responding for food on a modified DRL-30 sec schedule of reinforcement. Similar applications of norepinephrine were less effective than dopamine, while the anticholinesterase eserine depressed responding. Electrolytic lesions of the ventrolateral, but not the dorsomedial, prefrontal cortex of rats also increased their response rates. These results were interpreted as being consistent with the idea of a dopamine-acetylcholine antagonism in the VAS whose net output modulate behavioral inhibition. This striatal mechanism may be influenced by the ventrolateral prefrontal cortex.

Animals↗