Interaction with pups enhances dopamine release in the ventral striatum of maternal rats: a microdialysis study

A growing body of evidence suggests that an interference with dopamine (DA) transmission disrupts maternal behavior in the rat. The present brain microdialysis study was therefore conducted to investigate whether infants can modulate ventral striatal DA release in mother rats. There was a significant rise in the extracellular concentrations DA, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in the ventral striatum when mothers were reunited with their litters following separation overnight. Nursing was the predominant behavior during this phase of the experiment. More active behaviors were elicited by soiling pups with flowerpot earth, and this was accompanied by further increases in DA, DOPAC, HVA, and 5-HIAA. It is suggested that pup-induced stimulation of ventral striatal DA release facilitates parental responses such as pup retrieval.     

Dopamine D2-receptors regulate neurotensin release from nucleus accumbens and striatum as measured by in vivo microdialysis

The present study was undertaken to examine the role of dopamine D2-receptors in the regulation of neurotensin release. Through a modification of the methods described by Maidment et al. (Neuroscience, 45 (1991) 81-93), we have developed a highly reproducible method of measuring changes in extracellular NT in the striatum and nucleus accumbens by in vivo microdialysis in awake animals. It was observed that calcium-dependent release of NT was evoked in both structures by infusing a high concentration of potassium. In addition, systemic administration of the D2 agonist quinpirole (5 mg/kg) induced a rapid increase of approximately 200% in extracellular NT levels in the lateral caudate and 30-40% in the nucleus accumbens. Conversely, treatment with the D2 antagonist eticlopride (0.5 mg/kg) reduced extracellular NT in the medial anterior caudate and nucleus accumbens 20-30%, but had no effect in the lateral anterior caudate. These data demonstrate for the first time that D2-receptors are important in the dopaminergic regulation of extrapyramidal and limbic NT release in conscious animals.     

Dormia baskets impacted in the bile duct: release by extracorporeal shock-wave lithotripsy

BACKGROUND AND STUDY AIMS: Endoscopic extraction of bile duct stones may be complicated by impaction of the Dormia basket with captured stones, or rupture of the traction wire of the basket during mechanical lithotripsy. In an attempt to release impacted baskets by nonoperative means, we studied the efficacy of extracorporeal shock-wave lithotripsy in this dangerous clinical situation. PATIENTS AND METHODS: Fourteen extracorporeal shock-wave treatments were performed in 12 consecutive patients (eight women and four men; mean age 73.2 +/- 13.2 years, range 46-86 years) with an electrohydraulic shock-wave lithotriptor, using fluoroscopy (n = 13) or ultrasound (n = 1) for targeting. A total of 1845 +/- 334 (mean +/- SD) shock-wave discharges at a voltage of 22 +/- 4 kV were delivered per treatment. Nine treatment sessions (64%) were performed while patients were under general anesthesia. An attempt to extract the Dormia basket was made after disintegration of the captured stone had been confirmed by fluoroscopy. RESULTS: It was possible to remove the Dormia basket by nonsurgical means in 11 of the 12 patients (92%) after one treatment session, and after three treatment sessions in the remaining patient. Thus, disintegration of the stones allowed extraction of the Dormia basket in all patients. None of the patients needed surgical intervention. All patients were rendered free of bile duct stones after extracorporeal shock-wave lithotripsy and subsequent endoscopic removal of the fragments. No adverse effects of shock-wave therapy with subsequent extraction of the Dormia baskets were observed. CONCLUSION: Shock-wave therapy represents a primary nonsurgical therapeutic option in patients with either impacted Dormia baskets or broken devices which cannot be extracted by endoscopic means.     

Measurement of histamine release from human lung tissue ex vivo by microdialysis technique

OBJECTIVE AND DESIGN: Currently no method is available for measurement of mediator release from intact human lung. In this study, a microdialysis technique was used to measure histamine release from mast cells in human lung tissue ex vivo. MATERIAL: Microdialysis fibers of 216 microm were inserted into lung tissue and perfused with Krebs Ringer buffer at a rate of 3 microl/min. After a 15 min period of steady-state perfusion, anti-IgE and vehicle were injected into the lung tissue above individual fibers. Samples from each fibre were collected for 20 min at 2 min intervals. Histamine was assayed fluorometrically. RESULTS: Anti-IgE concentrations of 40-40,000 U/ml dose-dependently released histamine, significant histamine release being demonstrated with anti-IgE concentrations of 400 U/ml and greater. The kinetics of histamine release showed peak values 2-8 min after the injection. Great individual responses were observed but data could be reproduced within individual donors. Monocyte chemoattractant protein-1, a potent basophil secretagogue, did not induce histamine release in lung tissue which indicated mast cells to be the histamine source. Substance P did not release histamine in the lung tissue. CONCLUSIONS: The microdialysis technique allowed measurements of histamine release from mast cells in intact lung ex vivo. The method may prove useful since a number of experiments can be performed in a few hours in intact lung tissue without any dispersion or enzymatic treatment.     

The neurosteroid pregnenolone sulfate increases cortical acetylcholine release: a microdialysis study in freely moving rats

The effects of pregnenolone sulfate (Preg-S) administrations (0, 12, 48, 96, and 192 nmol intracerebroventricularly) on acetylcholine (ACh) release in the frontal cortex and dorsal striatum were investigated by on-line microdialysis in freely moving rats. Following Preg-S administration, extracellular ACh levels in the frontal cortex increased in a dose-dependent manner, whereas no change was observed in the striatum. The highest doses (96 and 192 nmol) induced a threefold increase above control values of ACh release, the intermediate dose of 48 nmol led to a twofold increase, whereas after the dose of 12 nmol, the levels of ACh were not different from those observed after vehicle injection. The increase in cortical ACh reached a maximum 30 min after administration for all the active doses. Taken together, these results suggest that Preg-S interacts with the cortical cholinergic system, which may account, at least in part, for the promnesic and/or antiamnesic properties of this neurosteroid.     

The role of ATP-sensitive potassium channels in striatal dopamine release: an in vivo microdialysis study

Inactivation of the retinoblastoma (RB) gene is known to be implicated in the pathogenesis of several types of human cancers. Since structural alterations of the RB gene have not been well examined in human bladder cancer, we looked for mutations in the entire coding region of this gene using polymerase chain reaction (PCR) and single-strand conformational polymorphism analysis of RNA. We also examined allelic loss of the RB gene using PCR-based restriction fragment length polymorphism analysis. Of 30 samples obtained from patients with bladder cancer, eight (27%) were found to have RB gene mutations. DNA sequencing of the PCR products revealed five cases with single point mutations and three cases with small deletions. These mutations included one (10%) of ten low-grade (grade 1) tumours, four (50%) of eight intermediate-grade (grade 2) tumours and three (25%) of 12 high-grade (grade 3) tumours. Likewise, mutations were found in four (21%) of 19 superficial (pTa and pT1) tumours and four (36%) of 11 invasive (pT2 or greater) tumours. In 15 informative cases, loss of heterozygosity at the RB locus was shown in five cases (33%), three cases with RB mutations and two without them. These results suggest that RB gene mutations are involved in low-grade and superficial bladder cancers as well as in high-grade and invasive cancers.     

Simultaneous measurement of opiate-induced histamine release in the periaqueductal gray and opiate antinociception: an in vivo microdialysis study

Histamine release and the subsequent activation of H2 receptors in the periaqueductal gray (PAG) are thought to be important components of morphine antinociception. In vivo microdialysis and antinociceptive testing were simultaneously applied in rats to characterize the effects of morphine on PAG histamine release and determine the relationship between histamine release and antinociception. In the absence of nociceptive (tail pinch) testing, morphine (12.8 mg/kg) induced a delayed, long-lasting release of histamine in the PAG. This effect of morphine was abolished by the opiate antagonist naltrexone (1 mg/kg) but was not mimicked by the mu-preferring agonist fentanyl (0.3 mg/kg), suggesting that activation of an opiate receptor other than, or in addition to, the mu receptor is necessary. In contrast to the findings with fentanyl in untested animals, fentanyl combined with nociceptive testing increased histamine release, even though testing alone had no such effect. Unexpectedly, tail pinch testing inhibited morphine-induced histamine release. These results show that the test procedure alters the action of opiates on histamine release, an effect likely to be the result of the stress of repeated tail pinch testing. Therefore, although histamine release may not be obligatory for all types of opiate antinociception, histamine in the PAG may function as a mediator of stress-induced potentiation of opiate antinociception. Even though the microdialysis technique has been acclaimed for its ability to assess neurochemical and behavioral characteristics simultaneously, the introduction of nociceptive testing clearly can alter the neurochemical systems under study.     

In vivo monitoring of gabapentin in rats: a microdialysis study coupled to capillary electrophoresis and laser-induced fluorescence detection

Gabapentin (GP) is a new anticonvulsant used in refractory epilepsy. Few studies have monitored the drug in vivo. We report the combination of capillary electrophoresis and laser-induced fluorescence detection (CZE-LIFD) with brain microdialysis and plasma ultrafiltration in an attempt to measure GP and offer an alternative technique for pharmacokinetic studies. We found that CZE-LIFD is capable of linearly measuring 10(-7)-10(-9) M GP in a 1 nL volume. It was also demonstrated that it is possible to monitor GP in prefrontal cortex dialysates and plasma in rats. It is concluded that the method permits in vivo monitoring of the drug in pharmacological as well as in clinical studies.     

Activation of non-NMDA receptors stimulates acetylcholine and GABA release from dorsal hippocampus: a microdialysis study in the rat

The effect of the non-N-methyl-D-aspartate (NMDA) agonists (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and quisqualate (QUIS) on the release of acetylcholine (ACh), gamma-amino butyric acid (GABA), aspartate (Asp) and glutamate (Glu) from the hippocampus of freely moving rats was studied by transversal microdialysis. Intracerebroventricular (i.c.v.) administration of the non-NMDA receptor agonist AMPA (0.5 nmol) enhanced (by about 200%) ACh release from the hippocampus. The effect of AMPA was completely antagonized by 6-nitro-7-sulphamoyl-benz(f)quinoxaline-2,3-dione (NBQX; 2 nmol, i.c.v). No effect was seen when AMPA was perfused through the septum. However, AMPA (200 microM) locally applied to the hippocampus, increased (by about 200%) ACh release. QUIS (200 microM) applied locally to the hippocampus produced a long-lasting increase in the release of ACh (by about 215%) and GABA (by about 460%). Local infusion of tetrodotoxin (1 microM) decreased ACh and GABA basal extracellular levels, and abolished the QUIS-induced increase in ACh and GABA. Our results demonstrate that non-NMDA glutamatergic receptors in the hippocampus regulate hippocampal release of GABA and ACh.     

Alterations in the opioid control of LHRH release from hypothalami isolated from aged male rats

Several lines of evidence have suggested that the opioid control of gonadotropin secretion in the male rat is altered with aging. Because neural control of gonadotropins is mediated through luteinizing hormone releasing hormone (LHRH) secreting neurons, we examined the postulated changes in the opioid control of gonadotropins more directly by studying isolated hypothalamic fragments in vitro. Hypothalami from young (75-90 days) and old (18-20 months) males were examined for their ability to release LHRH when incubated with increasing doses of naloxone in a semi-static culture system. Serum concentrations of testosterone and luteinizing hormone (LH) in the donor animals were both significantly lower in old male rats compared with young males. Basal secretion of LHRH was similar in both age groups. Two-way repeated measures ANOVA indicated that naloxone stimulated a significant dose-dependent increase in the release of LHRH into the media. ANOVA also indicated a significant effect of age. We conclude that the changes in the endogenous opioid systems reported to occur with aging are, in fact, linked to differences in LHRH secretion and thus to differences in the dynamic relationship between testosterone and LH in older male rats.     

Electrical stimulation of the prefrontal cortex increases cholecystokinin, glutamate, and dopamine release in the nucleus accumbens: an in vivo microdialysis study in freely moving rats

In vivo microdialysis, radioimmunoassay, and HPLC with electrochemical or fluorometric detection were used to investigate the release of cholecystokinin (CCK), glutamate (Glu), and dopamine (DA) in nucleus accumbens septi (NAS) as a function of ipsilateral electrical stimulation of medial prefrontal cortex (mPFC). CCK was progressively elevated by mPFC stimulation at 50-200 Hz. Stimulation-induced CCK release was intensity-dependent at 250-700 microA. NAS Glu and DA levels were each elevated by stimulation at 25-400 Hz; the dopamine metabolites DOPAC and homovanillic acid were increased by stimulation at 100-400 Hz. When rats were trained to lever press for mPFC stimulation, the stimulation induced similar elevations of each of the three transmitters to those seen with experimenter-administered stimulation. Perfusion of 1 mM kynurenic acid (Kyn) into either the ventral tegmental area (VTA) or NAS blocked lever pressing for mPFC stimulation. VTA, but not NAS, perfusion of Kyn significantly attenuated the increases in NAS DA levels induced by mPFC stimulation. Kyn did not affect NAS CCK or Glu levels when perfused into either the VTA or NAS. The present results are consistent with histochemical evidence and provide the first in vivo evidence for the existence of a releasable pool of CCK in the NAS originating from the mPFC. Although dopamine is the transmitter most closely linked to reward function, it was CCK that showed frequency-dependent differences in release corresponding most closely to rewarding efficacy of the stimulation. Although not essential for the reward signal itself, coreleased CCK may modulate the impact of the glutamatergic action in this behavior.     

Estrogen differentially modulates nicotine-evoked dopamine release from the striatum of male and female rats

BACKGROUND: Transluminal balloon angioplasty offers advantages to patch angioplasty. We evaluated the primary patency of thrombosed hemodialysis grafts that had undergone balloon angioplasty versus patch angioplasty as a salvage method. METHODS: We reviewed our experience with 22 consecutive intraoperative balloon angioplasties that were done in a 6-months period. The balloons used were noncompliant high pressure balloons. The balloon results were compared with those of 22 patients who had undergone patch angioplasties by the same surgeons. Age, gender, average time between graft insertion and revision, and number of prior revisions were analyzed. The two groups (patch and balloon) had similar ages (57 versus 58 years, respectively), gender distribution (12 women, 11 men versus 11 women and 11 men), average time of revisions before that particular procedure (15 versus 12 months), and average times of revisions before that procedure. RESULTS: Primary patencies of the patch and balloon group were respectively 86% versus 77% at 1 month, 45% versus 40% at 3 months, and 17% versus 28% at 6 months. There was no statistically significant difference between the two groups. Complications were comparable in both groups. CONCLUSION: Balloon angioplasty offers advantages to patch angioplasty, and we have shown similar patency rates. We recommend balloon angioplasty as a comparable method to salvage dialysis access grafts.     

Inhibitory effect of ketamine on depolarization-induced norepinephrine release in the rat ventral hippocampus investigated by in vivo microdialysis

The release of norepinephrine (NE) in the ventral hippocampus was studied in rats with microdialysis method. The basal release of NE with perfusion of normal artificial cerebrospinal fluid (ACSF) was 1.58 +/- 0.37 x 20 microliters-1 sample. The NE concentration increased significantly with perfusion of high potassium (60 mM) ACSF indicating that depolarization-induced release was up to 5 times higher than the basic level. Ketamine (20 mg.kg-1 and 80 mg.kg-1 im) significantly inhibited the depolarization-induced increase of NE, but did not affect the basal release. Neither 5 mg.kg-1 im of ketamine nor MK-801 had any effect on the basic or the depolarization-induced release. These results suggest that the inhibitory effect of ketamine on the depolarization-induced NE release was not due to the NMDA channel blocking properties of ketamine.     

Biotransformation of locally applied precursors of dopamine, serotonin and noradrenaline in striatum and hippocampus: a microdialysis study

In vivo microdialysis in freely moving rats was used to study the biotransformation, consisting primarily of decarboxylation by aromatic amino acid decarboxylase (AAAD), of the precursors L-3,4-dihydroxyphenylalanine (L-DOPA), L-5-hydroxytryptophan (L-5HTP), and L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) on extracellular levels of dopamine (DA), serotonin (5HT) and noradrenaline (NA), respectively. The precursors were administered locally through the microdialysis probe into the striatum and into the hippocampus. The different transmitter systems were compared with respect to the ability of the precursors to elevate extracellular levels of their associated transmitter. The basal extracellular concentrations of NA and DA were found to be tetrodotoxin (TTX, a blocker of fast sodium channels) sensitive in striatum and hippocampus, indicating the neuronal origin of the measured transmitters. The extracellular concentrations of 5HT (in hippocampus) were only 60% TTX-sensitive. L-DOPA and L-5HTP showed to be effective precursors of DA and 5HT, respectively, although their formation profile was quite different. The L-DOPA-induced increase in extracellular DA was large and short-lasting, while the L-5HTP-induced increase in 5HT was slower and less pronounced. The relative increase in extracellular DA or 5HT was more pronounced in the brain region where their baseline values were lower, but the absolute amount of transmitter formed from their precursor was similar in both brain regions. L-threo-DOPS was a poor precursor for NA and also failed to influence extracellular DA in striatum, questioning its use in the treatment of freezing gait in late stages of Parkinson's disease.     

Laparoscopic treatment of gallbladder and common bile duct stones: a prospective study

The aim of this study was to investigate prospectively the feasibility, success rate, safety, and short-term results of single-stage laparoscopic treatment of gallstones and ductal stones in 100 consecutive, unselected patients. Common bile duct (CBD) stones were diagnoses at routine intraoperative cholangiography and choledochoscopy in 100 of 950 patients with gallstones undergoing laparoscopic cholecystectomy (LC). Unsuspected CBD stones were present in 39 patients (4.1% of 950; 39% of 100); 26 patients were referred for surgery after failed endoscopic sphinctertomy (ES) performed elsewhere. Transcystic duct CBD exploration (TC-CBDE) was the procedure of choice. When it was not feasible, choledochotomy and direct CBD exploration (D-CBDE) was performed. Use of biliary drainage was liberal. A completion cholangiogram was obtained for all patients. Laparoscopic treatment of CBD stones was successful in 96 patients: after TC-CBDE in 63 and after D-CBDE in 33. Four operations were converted to open surgery (4%). Retained stones, observed in five patients, were treated by ES in two cases and by percutaneous endoscopic/fluoroscopic lithotripsy in three. Minor morbidity included biloma (n = 2), port site infection (n = 2), and subumbilical hematoma (n = 1). Major morbidity was bile leakage from the cystic duct stump in two cases due to clips or transcystic duct drainage displacement, respectively. One elderly, high risk patient died after being referred for several failed attempts of endoscopic clearance; she died from cardiogenic shock 3 days after successful laparoscopic treatment. Laparoscopic CBD exploration is feasible and safe in most patients, with short-term results that compare favorably with the results of sequential ES/LC reported in the literature.     

In vivo release of dopamine and its metabolites from rat striatum in response to domoic acid

The microdialysis technique was used to examine the effect of the neurotoxin domoate, an analog of glutamic acid, on striatal dopamine activity. Our results show that the intracerebral administration of different concentrations of domoate (100 and 500 microM) produced increases in the extracellular levels of dopamine associated to decreases in the extracellular levels of its metabolites dihydroxyphenylacetate and homovanillate from rat striatum. These changes seem to be related according to a time sequence, indicating a possible effect on the metabolism of dopamine. Changes were also observed in locomotor activity (cycling behavior, sniffing around and chewing) in rats during the domoate infusion. The physiological mechanism by which domoate increased dopamine release remains to be worked out.