Biomedical subjects

Q Pei

Publications and source records attributed to Q Pei.

25 records · Page 2Linked to original sources

PubMed1996

The nicotinic receptor agonists (-)-nicotine and isoarecolone differ in their effects on dopamine release in the nucleus accumbens.

This study compared the effect of the nicotinic receptor agonists, (-)-nicotine and isoarecolone, on the mesolimbic dopamine system of the rat using in vivo microdialysis. Previous studies showed that (-)-nicotine but not isoarecolone produced a locomotor activating effect, and that this was probably mediated by increased concentrations of dopamine in the nucleus accumbens. Nicotine (0.4 mg/kg s.c.) significantly increased extracellular concentrations of dopamine and of dihydroxyphenylacetic acid (DOPAC) by 75-80% in nucleus accumbens of rats. Isoarecolone (3.2-32 mg/kg s.c.) had no significant effect on either dopamine or DOPAC levels in this brain region and neither drug affected extracellular levels of 5-hydroxy indole acetic acid. Both nicotine and isoarecolone induced head-bobbing behaviour. Pretreatment with ketanserin reduced nicotine-induced head-bobbing suggesting a serotonergic mechanism. In conclusion, the absence of locomotor activation after administration of isoarecolone may be related to its failure to activate the mesolimbic dopamine system.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

5-HT efflux from rat hippocampus in vivo produced by 4-aminopyridine is increased by chronic lithium administration.

Effects of lithium on central 5-HT function have been shown using electrophysiological, behavioural and neurochemical approaches. Chronic lithium administration, for example, enhances both electrophysiological and behavioural responses mediated by postsynaptic 5-HT1A receptors as well as increasing potassium-evoked and electrically evoked release of 5-HT from the hippocampus in in vitro slices and in vivo. Our studies have shown that potassium-channel blocking drugs increase 5-HT release in vivo, and others have shown that lithium suppresses potassium currents in some cell types. We therefore investigated in the rat the effect of short-term (3 days) and long-term (21 days) lithium on 5-HT release evoked by potassium-channel blockade, using in vivo microdialysis. Long-term lithium treatment enhanced 5-HT efflux in rat hippocampus produced by 4-aminopyridine (4-AP) perfused in microdialysis fluid by as much as 100% within 40 min, compared with non-lithium-treated control rats. Short-term lithium treatment did not enhance 4-AP-induced 5-HT efflux. The effect of local tetraethylammonium chloride (TEA) on hippocampal 5-HT release was unaltered by long-term lithium treatment. In addition, neither the effect of local perfusion with 4-AP on efflux of striatal 5-HT, or dopamine in nucleus accumbens, was altered by chronic lithium treatment. These results show that long-term lithium treatment enhances 4-AP-stimulated efflux of 5-HT in the hippocampus, but not in the striatum, nor dopamine output in the nucleus accumbens.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗

PubMed1993

Quinine and 4-aminopyridine inhibit the stimulatory output of dopamine in nucleus accumbens and the behavioural activity produced by morphine.

We have tested the effects in rats of two potassium channel blocking drugs, 4-aminopyridine and quinine, on morphine-induced stimulation of behavioural activity and on dopamine outflow in nucleus accumbens using microdialysis. Morphine (1 mg/kg s.c.) increased dopamine output by 123% in nucleus accumbens. This dose of morphine also stimulated behavioural activity which in the early part of the time course corresponded closely with the increase of dopamine outflow in nucleus accumbens. Both of these effects were maximal 60-80 min after the morphine administration. 4-Aminopyridine (1 mg/kg i.p.) or quinine (50 mg/kg i.p.) injected 20 min before morphine inhibited the maximal effect on dopamine output by 88 and 80% respectively. Pretreatment with the two potassium channel blocking drugs also resulted in a reduction of morphine-induced stimulation of behavioural activity, 4-aminopyridine by 77% and quinine by 66%. In summary this study demonstrates that two drugs known to block potassium channels inhibit two effects of morphine associated with mesolimbic dopamine function.

4-Aminopyridine↗

PubMed1993

5-HT3 receptor antagonists inhibit morphine-induced stimulation of mesolimbic dopamine release and function in the rat.

The effects of three different 5HT3 receptor antagonists, granisetron, ICS 205-930 and ondansetron (0.01, 0.1 and 1 mg/kg, s.c.) were tested on changes in mesolimbic dopamine function produced by 1 mg/kg of morphine in the rat. Increases of in vivo dopamine release and stimulation of behavioural activity (grooming, locomotion, rearing and sniffing) were monitored. Morphine (0.5 and 1 mg/kg, s.c.) increased dose-dependently the concentration of dopamine in dialysates obtained from the nucleus accumbens. This action of morphine was inhibited by the opiate antagonist naloxone (1 mg/kg, s.c.). Morphine (0.5 and 1 mg/kg) stimulated behavioural activity, which in the early part of the time course corresponded closely with the increase of dopamine in the nucleus accumbens. Pretreatment with 1 mg/kg (s.c.) of granisetron resulted in moderate inhibition (28%) of the morphine-induced stimulation of the extracellular dopamine levels, while doses of 0.01 and 0.1 mg/kg (s.c.) had no effect. The highest dose of granisetron (1 mg/kg, s.c.) also significantly reduced the morphine-induced enhancement of behavioural activity. The fact that granisetron attenuated morphine-induced effects on mesolimbic DA only at the highest dose tested (1 mg/kg, s.c.) was also true for ICS 205-930 and ondansetron. It is concluded that 5HT3 receptor antagonists partially inhibit, with low potency, the morphine-induced stimulation of dopamine release in the nucleus accumbens and the corresponding behavioural activation.

Animals↗

PubMed1990

In vivo neurochemical effects of tail pinch.

Tail pinch in the rat gives rise to a well characterised pattern of behaviour which includes gnawing, licking and eating. We have used both in vivo voltammetry and microdialysis to monitor neurochemical changes which accompany the behavioural response to a 5-min tail pinch. Tail pinch resulted in a increase of extracellular 5-hydroxytryptamine and a smaller and more delayed increase of 5-hydroxyindole acetic acid in the hippocampus. In the striatum there was a rise of both extracellular dopamine and ascorbate. With a recently developed constant potential voltammetric technique we can continuously monitor changes in extracellular ascorbate. Using this technique we found a very rapid rise in ascorbate current during a 5-min tail pinch; the current began to decline as soon as the clip was removed. The high time resolution of the technique also allowed us to record similar ascorbate changes during a 0.5-s tail pinch.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Tail pinch-induced changes in the turnover and release of dopamine and 5-hydroxytryptamine in different brain regions of the rat.

Tail pinch was administered through a paper clip attached to the rat's tail. The ex vivo changes in the metabolite/transmitter ratio were used as a measure of changes in the turnover of dopamine and 5-hydroxytryptamine. After a 2-min tail pinch dopamine turnover was increased in the striatum but not in the frontal cortex, hypothalamus or olfactory tubercle; 5-hydroxytryptamine turnover was increased in frontal cortex and hippocampus and was unchanged in striatum, hypothalamus and olfactory tubercle. Microdialysis was used to monitor the changes in extracellular neurotransmitter and metabolite concentrations during and after tail pinch. A 5-min tail pinch caused a rapid rise of both dopamine in the striatum and 5-hydroxytryptamine in the hippocampus. There was a smaller increase in the 5-hydroxytryptamine metabolite 5-hydroxyindoleacetic acid and only a non-significant increase in the dopamine metabolite 3,4-dihydroxyphenylacetic acid.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1989

Both systemic and local administration of benzodiazepine agonists inhibit the in vivo release of 5-HT from ventral hippocampus.

The effects of benzodiazepine- and GABAA-receptor agonists and antagonists on the release and metabolism of 5-HT were measured in the ventral hippocampus of freely moving rats using microdialysis. Systemic injections of the benzodiazepine agonists, flurazepam and diazepam reduced the levels of 5-HT while the partial inverse agonist, FG 7142 (N-methyl-beta-carboline-3-carboxamide), had no effect. Local perfusion of flurazepam through the dialysis probe also decreased the release of 5-HT in the ventral hippocampus, an effect which was completely blocked by the benzodiazepine antagonist, Ro15-1788 (flumazenil). Local application of the GABAA agonist muscimol had no effect on the release of 5-HT, while the antagonist picrotoxin, administered locally, caused a 4-fold enhancement of release of 5-HT. Picrotoxin also resulted in a complete block of the inhibitory effect of flurazepam on release of 5-HT. None of these drugs caused significant changes in the levels of the metabolite of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) in the ventral hippocampus. These results suggest that the inhibitory effect of flurazepam on the release of 5-HT is mediated by benzodiazepine/GABAA receptors in the hippocampus and that GABA exerts a tonic inhibitory effect on the release of 5-HT in the region of the brain.

Animals↗