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T Sharp

Publications and source records attributed to T Sharp.

At least 73 records · Page 4Linked to original sources
PubMed1997

Enhancement of dopamine-mediated behaviour by the NMDA antagonists MK-801 and CPP: similarities with repeated electroconvulsive shock.

The behavioural effect of dopamine D1-like receptor agonists (SKF 38393, SKF 81297) and a D2-like receptor agonist (quinpirole), administered alone and in combination, was tested in rats pretreated with a single injection of an NMDA antagonist (MK-801, CPP) or vehicle. Agonist-induced behaviour was monitored by automated activity meters and direct observation using a checklist scoring method. Pretreatment with MK-801 (0.05 mg/kg, SC, 30 min) had no significant effect (compared to controls) on the behavioural response to SKF 38393 (7.5 mg/kg SC), SKF 81297 (0.2 mg/kg SC) or quinpirole (0.1 and 0.25 mg/kg SC) administered alone. In contrast, MK-801 markedly increased locomotion (activity counts and scores) induced by co-administration of a D1-like plus a D2-like agonist [SKF 38393 (7.5 mg/kg) plus quinpirole (0.25 mg/kg), SKF 81297 (0.2 mg/kg) plus quinpirole (0.1 mg/kg)]. The behavioural response to the non-selective dopamine agonist apomorphine (0.5 mg/kg SC) was also enhanced by MK-801. Pretreatment with CPP (0.1 mg/kg SC, 30 min) also significantly increased the locomotor response to co-administration of SKF 38393 plus quinpirole administered alone, but had no effect on the behavioural response to separate injection of these agonists. MK-801 (0.05 mg/kg SC, 30 min) also enhanced the behavioural response to bilateral injection into the nucleus accumbens of SKF 38393 plus quinpirole (1.0 plus 0.4 microgram/side, respectively). These data suggest that in the intact rat, the enhancement of dopamine-mediated behaviour by either MK-801 or CPP requires concomitant stimulation of D1-like and D2-like receptors, possible located within the nucleus accumbens. The effect of these NMDA antagonists on dopamine function is similar to that of repeated electroconvulsive shock (ECS), indicating that one of the actions of ECS may be to reduce NMDA receptor function.

Animals↗
PubMed1997

Critical issues in the antisense inhibition of brain gene expression in vivo: experiences targetting the 5-HT1A receptor.

There have been many recent reports of receptor down-regulation in the brain by antisense oligodeoxynucleotides (ODNs) administered in vivo. However, the literature is inconsistent regarding the experimental criteria that are necessary or sufficient to demonstrate a true antisense effect. Here we review some of the critical conceptual and methodological issues. We highlight the problems of specificity and toxicity encountered in our attempts to down-regulate the 5-HT1A receptor using a phosphorothioate-modified ODN. We also present preliminary data suggestive of a decreased hippocampal 5-HT1AR expression induced by the antisense ODN, but it is a reduction which is of limited extent and which does not provide unequivocal evidence for an antisense-mediated effect. We conclude that antisense ODNs are not yet suitable as tools for routine in vivo neuropharmacological use, although they show considerable promise.

Analysis of Variance↗
PubMed1997

Effect of a selective 5-HT reuptake inhibitor in combination with 5-HT1A and 5-HT1B receptor antagonists on extracellular 5-HT in rat frontal cortex in vivo.

1. Selective 5-hydroxytryptamine (5-HT; serotonin) reuptake inhibitors (SSRIs) cause a greater increase in extracellular 5-HT in the forebrain when the somatodendritic 5-HT1A autoreceptor is blocked. Here, we investigated whether blockade of the terminal 5-HT1B autoreceptor influences a selective 5-HT reuptake inhibitor in the same way, and whether there is an additional effect of blocking both the 5-HT1A and 5-HT1B autoreceptors. 2. Extracellular 5-HT was measured in frontal cortex of the anaesthetized rat by use of brain microdialysis. In vivo extracellular recordings of 5-HT neuronal activity in the dorsal raphe nucleus (DRN) were also carried out. 3. The selective 5-HT reuptake inhibitor, paroxetine (0.8 mg kg-1, i.v.), increased extracellular 5-HT about 2 fold in rats pretreated with the 5-HT1A receptor antagonist, WAY100635. When administered alone neither paroxetine (0.8 mg kg-1, i.v.) nor WAY100635 (0.1 mg kg-1, i.v.) altered extracellular 5-HT levels. 4. Paroxetine (0.8 mg kg-1, i.v.) did not increase 5-HT in rats pretreated with the 5-HT1B/D receptor antagonist, GR127935 (1 mg kg-1, i.v.). GR127935 (1 and 5 mg kg-1, i.v.) had no effect on extracellular 5-HT when administered alone. 5. Interestingly, paroxetine (0.8 mg kg-1, i.v.) caused the greatest increase in 5-HT (up to 5 fold) when GR127935 (1 or 5 mg kg-1, i.v.) was administered in combination with WAY100635 (0.1 mg kg-1, i.v.). Administration of GR127935 (5 mg kg-1, i.v.) plus WAY100635 (0.1 mg kg-1, i.v.) without paroxetine, had no effect on extracellular 5-HT in the frontal cortex. 6. Despite the lack of effect of GR127935 on 5-HT under basal conditions, when 5-HT output was elevated about 3 fold (by adding 1 microM paroxetine to the perfusion medium), the drug caused a dose-related (1 and 5 mg kg-1, i.v.) increase in 5-HT. 7. By itself, GR127935 slightly but significantly decreased 5-HT cell firing in the DRN at higher doses (2.0-5.0 mg kg-1, i.v.), but did not prevent the inhibition of 5-HT cell firing induced by paroxetine. 8. In summary, our results suggest that selective 5-HT reuptake inhibitors may cause a large increase in 5-HT in the frontal cortex when 5-HT autoreceptors on both the somatodendrites (5-HT1A) and nerve terminals (5-HT1B) are blocked. This increase is greater than when either set of autoreceptors are blocked separately. The failure of a 5-HT1B receptor antagonist alone to enhance the effect of the selective 5-HT reuptake inhibitor in our experiments may be related to a lack of tone on the terminal 5-HT1B autoreceptor due to a continued inhibition of 5-HT cell firing. These results are discussed in relation to the use of 5-HT autoreceptor antagonists to augment the antidepressant effect of selective 5-HT reuptake inhibitors.

Animals↗
PubMed1997

Functional mapping of dorsal and median raphe 5-hydroxytryptamine pathways in forebrain of the rat using microdialysis.

Recent neurochemical studies of the properties of 5-hydroxytryptamine (5-HT) pathways arising from the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN) have measured extracellular 5-HT in brain regions with reported preferential DRN or MRN 5-HT inputs. Here, we have tested whether electrical stimulation of the DRN and MRN releases 5-HT in rat forebrain regions in a pattern that fits the reported distribution of DRN/MRN pathways. The effect on extracellular 5-HT of electrical stimulation (5 Hz, 300 microA, 20 min) of the DRN, and then MRN, was determined in six regions of the anaesthetised rat. Stimulation of the DRN evoked a short-lasting but clear-cut release of 5-HT (+70-100%) in regions (frontal cortex, dorsal striatum, globus pallidus, and ventral hippocampus) reported to receive a 5-HT projection from the DRN. Regions receiving an MRN innervation (dorsal hippocampus, medial septum, and ventral hippocampus) released 5-HT (+70-100%) in response to MRN stimulation. Regions reported to receive a preferential DRN innervation (frontal cortex, dorsal striatum, and globus pallidus) did not respond to MRN stimulation. Of two regions (dorsal hippocampus and medial septum) reported to receive a preferential MRN innervation, one did not respond to DRN stimulation (dorsal hippocampus) although the other (medial septum) did. In summary, electrical stimulation of the DRN and MRN released 5-HT in a regionally specific pattern. With the exception of one region (medial septum), this pattern of release bears a strong relationship to the distribution of 5-HT projections from the DRN and MRN reported by anatomical studies. The combination of raphe stimulation with microdialysis may be a useful way to study the in vivo neurochemistry of DRN/MRN 5-HT pathways.

Animals↗
PubMed1997

A study of attachment loss patterns in survivor teeth at 18 months, 36 months and 5 years in community-dwelling older adults.

Most of our knowledge regarding the natural history of periodontitis in adults has come from clinical studies of dental patients. However, it is known that dental patients usually are not representative of what actually happens in the population. This paper presents population-based attachment loss trends in survivor teeth to address the following issues; 1) whether attachment loss during 1 period in time is associated with higher risk for attachment loss at a subsequent period in the same subject; 2) whether sites in survivor teeth with deeper periodontal pockets at baseline are more likely to experience future attachment loss; and 3) whether the effect of regular use of dentists' services on attachment loss are demonstrated in a community-dwelling population. In 1988, the University of North Carolina School of Dentistry initiated the Piedmont 65+ Dental Study, which was designed to elicit 800 dentate respondents in the 5-county area who were examined again at 18, 36 and 60 months. Our findings indicated that, for the 3 time periods investigated, attachment loss during the first period was not related to the incidence of attachment loss at a subsequent period for most people. However, for people who experience multiple episodes, the second episode was likely to immediately follow the first episode. This pattern did not occur at the site level where no site experienced more than 2 successive episodes, and a previous episode did not put a site at higher risk for a subsequent episode. Our data also indicated that both baseline pocket depth and irregular dental visits were positively associated with the proportion of sites that demonstrated break-down over the next 5 yr.

Aged↗
PubMed1997

A 5-year study of attachment loss and tooth loss in community-dwelling older adults.

Tooth loss is a widely recognized endpoint measure for the effects of periodontal diseases and the impact of periodontal therapy. In fact, traditional clinical measures of periodontal status often are considered to be surrogate endpoints in that they are assumed to be related to tooth loss. However, the strength of the relationship between attachment loss and tooth loss in a representative population of untreated subjects has not been studied extensively. The purpose of this paper is to present the trends in attachment loss over a 5-yr period in a population of community-dwelling elderly blacks and whites. Specifically, this paper presents attachment loss trends both at the person and tooth level to address the following issues; 1) whether teeth that experience attachment loss during 1 time period are more likely to be lost at the next time period; and 2) given similar levels of attachment loss, why are some people more likely to lose teeth? In 1988, the University of North Carolina School of Dentistry initiated the Piedmont 65+ Dental Study, which was designed to elicit 800 dentate respondents in the 5-country area who were examined again at 18, 36 and 60 months. Our findings indicated that teeth with poorer attachment level at baseline had a higher probability of being lost during the next 5 yr and teeth that experienced attachment loss during a time period were more likely to be lost during the next time period than teeth without additional attachment loss. In addition, it appears that there are person-level characteristics associated with increasing tendency towards tooth loss in people with similar periodontal status, a finding that may clarify the relationship between attachment loss and tooth loss.

Activities of Daily Living↗
PubMed1996

Burst-firing activity of presumed 5-HT neurones of the rat dorsal raphe nucleus: electrophysiological analysis by antidromic stimulation.

We recently reported raphe neurones which frequently fired spikes in short bursts. However, the action potentials were broad and the neurones fired in a slow and regular pattern, suggesting they were an unusual type of 5-hydroxytryptamine (5-HT) neurone. In the present study, we investigated whether these putative burst-firing 5-HT neurones project to the forebrain and whether all spikes fired in bursts propagate along the axon. In anaesthetised rats, electrical stimulation of the medial forebrain bundle evoked antidromic spikes in both burst-firing neurones and in single-spiking, classical 5-HT neurones recorded in the dorsal raphe nucleus. Although the antidromic spike latency of the single-spiking and burst-firing neurones showed a clear overlap, burst-firing neurones had a significantly shorter latency than single-spiking neurones. For both burst-firing neurones and classical 5-HT neurones, antidromic spikes made collisions with spontaneously occurring spikes. Furthermore, in all burst-firing neurones tested, first, second and third order spikes in a burst could be made to collide with antidromic spike. Interestingly, in a small number of burst-firing neurones, antidromic stimulation evoked spike doublets, similar to those recorded spontaneously. From these data we conclude that burst-firing neurones in the dorsal raphe nucleus project to the forebrain, and each spike generated by the burst propagates along the axon and could thereby release transmitter (5-HT).

Action Potentials↗
PubMed1996

8-OH-DPAT-induced release of hippocampal noradrenaline in vivo: evidence for a role of both 5-HT1A and dopamine D1 receptors.

Here we investigate the effects of the novel selective 5-HT1A receptor antagonist, N-[2-[4-(2 methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl cyclo-hexanecarboxamide (WAY 100635), and the dopamine D1 receptor antagonist, R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin++ +-7-ol (SCH 23390), on the increase in extracellular noradrenaline in rat hippocampus induced by the 5-HT1A receptor agonist, 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT). 8-OH-DPAT (0.1 and 1 mg/kg s.c.) caused a dose-related increase in extracellular noradrenaline. WAY 100635 (0.3 and 1 mg/kg s.c.) did not block the release of noradrenaline induced by the higher dose of 8-OH-DPAT (1 mg/kg s.c.) but abolished the response to the lower dose (0.1 mg/kg s.c.). When administered alone, WAY 100635 (0.3 and 1 mg/kg s.c.) had no effect on extracellular noradrenaline. The postsynaptically mediated 5-HT behavioural syndrome induced by the higher dose of 8-OH-DPAT, in contrast to the increase in noradrenaline, was completely blocked by WAY 100635 (0.3 mg/kg s.c.). Finally, the noradrenaline response to 8-OH-DPAT (0.1 mg/kg s.c.) was blocked by SCH 23390 (0.5 mg/kg s.c.). Our data confirm that noradrenaline can be released by activation of 5-HT1A receptors but show that these receptors are not tonically activated, and may be more sensitive to stimulation than classical postsynaptic 5-HT1a receptors. A role for the dopamine D1 receptor in the noradrenaline response to 8-OH-DPAT is also suggested.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Intracellular recordings from burst-firing presumed serotonergic neurones in the rat dorsal raphe nucleus in vivo.

Here we report the existence of burst-firing neurones in the rat dorsal raphe as detected in vivo using intracellular electrophysiological techniques. These neurones discharged single action potentials and doublets or triplets of action potentials in a slow and regular pattern. The apparent input resistance, action potential width and firing threshold of these burst-firing raphe neurones were indistinguishable from classical 5-HT neurones. Spike doublets were evoked by depolarising DC currents, but only in burst-firing neurones. These findings provide further evidence to support the hypothesis that 5-HT neurones (or a sub-set of them) are capable of burst-firing activity.

Action Potentials↗
PubMed1996

A 5-hydroxytryptamine lesion markedly reduces the incidence of burst-firing dorsal raphe neurones in the rat.

Recently, we described neurones in the rat dorsal raphe nucleus (DRN) with electrophysiological characteristics typical of 5-hydroxytryptamine (5-HT) neurones except that the neurones fired brief bursts. Here we report the effect of 5-HT lesions on the incidence of these burst-firing neurones. In vivo extracellular recordings revealed that in rats pretreated with the selective 5-HT neurotoxin, 5,7-dihydroxytryptamine, the occurrence of typical 5-HT neurones was significantly decreased (80%) compared to controls. In these 5-HT lesioned animals, the number of the burst-firing DRN neurones was also significantly reduced (91%). Neurones previously characterised as not containing 5-HT, were not altered by the lesion. These data are further evidence to support our hypothesis that burst-firing neurones in the DRN contain 5-HT.

5,7-Dihydroxytryptamine↗
PubMed1996

The role of 5-HT1A autoreceptors and alpha 1-adrenoceptors in the inhibition of 5-HT release--II NAN-190 and SDZ 216-525.

Novel 5-HT1A receptor antagonists, WAY 100135 and WAY 100635, were used to test the involvement of 5-HT1A receptors in the decrease of hippocampal extracellular 5-HT induced by the 5-HT1A/alpha 1 ligands, NAN-190 and SDZ 216-525. Using microdialysis in anaesthetized rats, it was found that WAY 100135 (3 mg/kg s.c.) and WAY 100635 (0.3 mg/kg s.c.) antagonised the decrease of 5-HT induced by the 5-HT1A receptor agonist 8-OH-DPAT (0.025 mg/kg s.c.) but did not alter 5-HT when administered alone. Both NAN-190 (0.03 and 0.3 mg/kg s.c.) and SDZ 216-525 (1 mg/kg s.c.) decreased 5-HT. The effect of 0.03 mg/kg s.c. NAN-190 was antagonised by WAY 100135 (3 mg/kg s.c.) and WAY 100635 (0.3 mg/kg s.c.). The effect of SDZ 216-525 (1 mg/kg s.c.) was also blocked by WAY 100635 (0.3 mg/kg s.c.). However, the 5-HT response to a high dose of NAN-190 (0.3 mg/kg s.c.) was not antagonised by WAY 100635 (0.3 or 3 mg/kg s.c.). Our experiments using WAY 100635 and WAY 100135 provide clear evidence that NAN-190 and SDZ 216-525 act as agonists at the 5-HT1A autoreceptor, supporting our earlier studies using the non-selective 5-HT1A antagonist, pindolol. However, our data reveal that, at least in the case of NAN-190, non-5-HT1A receptor mechanisms mediate the decrease of 5-HT induced by higher doses. A lack of specificity of NAN-190 (and possibly SDZ 216-525) at high doses may explain the failure of previous studies to detect a 5-HT1A receptor agonist action.

Animals↗
PubMed1996

Effects of repeated administration of 3,4-methylenedioxymethamphetamine on 5-hydroxytryptamine neuronal activity and release in the rat brain in vivo.

In experimental animals, administration of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) leads to extensive, but incomplete, loss of 5-hydroxytryptamine (5-HT) innervation in the brain. Here, we report the effects of MDMA on 5-HT neuronal function measured in the rat in vivo using electrophysiological and microdialysis techniques. Two weeks after administration of an established neurotoxic regimen of MDMA (20 mg/kg s.c., twice daily for 4 days) we found; 1) no change in either the density or the firing activity of 5-HT neurons in the dorsal raphé nucleus; 2) no change in basal extracellular 5-HT in either the frontal cortex or the hippocampus, although extracellular 5-hydroxyindoleacetic acid was reduced by about 50% in both regions; and 3) no change in the amount of 5-HT released in the hippocampus in response to electrical stimulation (5 Hz) of either the dorsal or medial raphé nucleus, but a marked reduction in the amount of 5-HT released in the frontal cortex after electrical stimulation of the dorsal raphé nucleus. In summary, although MDMA causes marked 5-HT neurotoxicity, our data suggest that 5-HT cell firing is unchanged and, furthermore, that 5-HT release is maintained in some (but not all) forebrain regions even in response to physiological levels of stimulation.

Animals↗
PubMed1996

The effect of prolonged pneumoperitoneum on renal function in an animal model.

BACKGROUND: Prolonged, increased intra-abdominal pressure (IAP) during laparoscopic surgery has been associated with oliguria and anuria. STUDY DESIGN: The objective of this study was to evaluate the effects of various levels of IAP on renal function. Ten groups of three adult female farm pigs were given a general anesthetic, followed by establishment of an IAP of 0, 5, 10, 15, or 20 mm Hg with CO2, 20 mm Hg with argon gas, abdominal wall lift device, renal vein occlusion (RVO), 15 mm Hg with CO2 plus dopamine administration at 2 microgram/kg/minute, or 20 mm Hg retroperitoneal CO2 insufflation. The following studies were recorded: baseline central venous pressure (CVP), pulmonary wedge pressure (PWP), cardiac output (CO), renal vein flow (RVF), renal artery pressure (RAP), selective urine output (UO), urinary osmolarity, and creatinine clearance; the parameters were repeated every 30 minutes for the four hours of the IAP study and two hours after release of the IAP. RESULTS: The results were analyzed within two main IAP groups: less than 15 mm Hg and greater than or equal to 15 mm Hg. There was no clinically significant variation in the CVP, PWP, and RAP. The CO decreased slightly and this was more significant in the greater than or equal to 15 mm Hg group. The RVF and UO decreased concomitantly and significantly in the greater than or equal to 15 mm Hg group. Even after two hours of desufflation, the RVF did not return to baseline, although the UO improved. Creatinine clearance decreased significantly in the greater than or equal to 15 mm Hg group. The RVO group exhibited similar changes in the study parameters as those seen in the greater than or equal to 15 mm Hg group, although the RVF did not improve on release of the renal vein in the RVO group. Changes were the same with an argon or CO2 IAP of 20 mm Hg. The abdominal wall lift device had an associated decrease in RVF at 15 KG force but no alteration in UO. Retroperitoneal insufflation resulted in the same decrease in RVF and UO as seen with the same IAP. Dopamine did not afford a protective effect on UO during an IAP of 15 mm Hg. CONCLUSIONS: The decreased UO during prolonged IAP greater than or equal to 15 mm Hg in the animal model is associated with a corresponding decrease in RVF, but does not appear to be associated with any permanent renal derangement nor any transient histologic changes.

Animals↗
PubMed1996

Evaluation of a two-site immunoradiometric assay for measuring noncomplexed (free) prostate-specific antigen.

Serum prostate-specific antigen (PSA) in men is present as two different molecular forms separable by gel-filtration chromatography (GFC). We have evaluated a two-site IRMA that measures only the noncomplexed (free) form of PSA (F-PSA). Verification that the F-PSA assay measures solely F-PSA was obtained by assaying GFC-fractionated serum samples with both the F-PSA IRMA and a commercial PSA assay that measures total PSA (T-PSA: F-PSA plus alpha 1-antichymotrypsin-complexed PSA). The F-PSA assay detected only the 30-kDa peak corresponding to the free form of PSA, whereas the T-PSA assay detected two peaks: complexed PSA at approximately 90 kDa and F-PSA at approximately 30 kDa. The F-PSA assay had an analytical detection limit of 0.03 microgram/L and a measuring range up to 50 micrograms/L. The intraassay CV was 1.7-10% in the concentration range of 0.2-30 micrograms/L. The interassay CV was 3.4-12.5% in the same concentration range. Dilution and recovery studies showed no significant deviation from linearity across the assay range. The assay was insensitive to interference from hemoglobin, bilirubin, and total lipids up to concentrations of 5, 0.2, and 10 g/L, respectively. No significant loss of immunological activity (analyte stability) was seen day-to-day ( < or = 5) or after repeated freeze/thaw ( < or = 5) cycles. We conclude that the F-PSA IRMA is an accurate, precise, and reliable tool for measuring F-PSA in human serum.

Aged↗
PubMed1995

Repeated ECS differentially affects rat brain 5-HT1A and 5-HT2A receptor expression.

We investigated the effect of electroconvulsive shock (ECS), administered five times over 10 days, on 5-HT1A and 5-HT2A receptor mRNA and binding site densities in the rat brain using in situ hybridization histochemistry and quantitative autoradiography. ECS treatment increased 5-HT1A receptor mRNA abundance and binding site densities in the dentate gyrus, but decreased these parameters in the CA3c layer of the hippocampus. No changes in 5-HT1A receptor mRNA and binding sites occurred in other hippocampal subfields, neocortex or raphe nuclei. Repeated ECS was also found to increase 5-HT2A receptor binding site densities in the neocortex and this was accompanied by a non-significant increase in cortical 5-HT2A receptor mRNA abundance. Our study demonstrates that in the rat, repeated ECS produces anatomically and molecularly discrete effects on 5-HT1A and 5-HT2A receptor gene expression. These changes may be relevant to the therapeutic effect of repeated ECS in depression.

Animals↗
PubMed1995

Multiple laboratory comparison of the doubly labeled water technique.

A double-blind study was conducted to determine between-laboratory variability in the doubly labeled water method for measurement of total energy expenditure in humans, and to compare the accuracy and precision of three widely-used procedures for calculating rates of carbon dioxide production from the original isotope data. Eighteen laboratories from five countries participated in the study. All laboratories were provided with five water standards containing varying amounts of 2H and 18O, and in addition 11 laboratories were provided with urine and dose specimens from one (six laboratories) or two (five laboratories) healthy elderly subjects of normal height and weight undergoing a calorimetric validation of the doubly labeled water method. The data from the five water standards were analyzed to predict between-laboratory variability in the doubly labeled water technique in all laboratories. In addition, data from the subjects were analyzed using the "slope-intercept", "2-point" and "modified" methods of calculation. The results confirm that the doubly labeled water method can be an accurate technique for the measurement of energy expenditure in adult human subjects in some laboratories. However, there was substantial between-laboratory variability in the results and some laboratories returned physiologically impossible results. There was no significant effect of calculation procedure on the accuracy of the technique in this limited comparison, although the slope-intercept procedure appeared to be more susceptible to analytical error than the other procedures. The isotope standards analyzed by participants in this study will be made available to other investigators on request.

Aged↗
PubMed1995

Inhibition of median and dorsal raphe neurones following administration of the selective serotonin reuptake inhibitor paroxetine.

Acute systemic injection of selective serotonin reuptake inhibitors (SSRIs) decreases 5-HT neuronal firing in the dorsal raphe nucleus (DRN). Recent data, however, question whether these drugs also inhibit the firing of 5-HT neurones in the median raphe nucleus (MRN). Using in vivo extracellular electrophysiological recording techniques in the chloral hydrate anaesthetised rat, we have tested the effect of acute administration of the SSRI, paroxetine, on 5-HT neuronal activity in the MRN and DRN. Presumed 5-HT neurones in the MRN displayed the same electrophysiological characteristics as those in the DRN, the only detectable difference being that MRN neurones showed a significantly (p < 0.001) slower mean (+/- SEM(n)) spontaneous firing rate (MRN, 5.6 +/- 0.9 (14) spikes/10 s; DRN, 13.5 +/- 1.6 (24) spikes/10 s). Paroxetine caused a dose-related (0.1-0.8 mg/kg i.v.) inhibition of all MRN neurons tested (n = 8), producing a complete cessation of cell-firing at the highest doses. DRN neurones (n = 9) responded in a similar fashion. Furthermore, paroxetine inhibited MRN and DRN neurones with almost identical potency (MRN ED50 259 +/- 57 micrograms/kg i.v.: DRN ED50 243 +/- 49 micrograms/kg i.v.). In the majority of cells tested, the effect of paroxetine was reversed by the 5-HT1A receptor antagonists spiperone or (+)WAY100135, implicating the involvement of the 5-HT1A autoreceptor. The selective 5-HT1A receptor agonist 8-OH-DPAT also inhibited the firing of MRN (n = 5) and DRN (n = 12) neurones and with equal potency (MRN ED50, 1.32 +/- 0.40 microgram/kg i.v.: DRN ED50, 1.19 +/- 0.23 microgram/kg i.v.).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗