PubMed Health⌕ Search

Biomedical subjects

P Alster

Publications and source records attributed to P Alster.

At least 19 recordsLinked to original sources
PubMed2001

Microdialysis of galanin in rat spinal cord: in vitro and in vivo studies.

The release of the neuropeptide galanin was measured with microdialysis in the dorsal horn of the rat spinal cord. Recovery of unlabeled galanin-like immunoreactivity (GAL-LI) in vitro was measured with radioimmunoassay (RIA) and was found to be 1.4-1.5%. In vivo galanin level was close to the detection level of the RIA under basal conditions. The peptide was released in the dorsal horn during electrical stimulation of the sciatic nerve. The nerve was stimulated for 30 min at a stimulus strength that activated A- and C-fibers. Thus, release of galanin in the spinal cord of the rat is possible to measure with the microdialysis technique.

Animals↗
PubMed2001

Increased level of cholecystokinin in cerebrospinal fluid is associated with chronic pain-like behavior in spinally injured rats.

Cholecystokinin (CCK) is a physiological antagonist of opioid-mediated antinociception and may be involved in some chronic pain states where opioids have reduced effect. We have previously shown in a rat model of central neuropathic pain after spinal cord injury that blockade of CCK-B receptors lead to marked pain relief. In the present study, we showed that spinally injured rats exhibiting chronic pain-like behaviors (aversive reaction to innocuous mechanical and cold stimulation) had significantly elevated level of CCK-like immunoreactivity in cerebrospinal fluid compared to normal rats or spinally injured rats which did not exhibit pain-like behaviors. The increased level of circulating CCK in the cerebrospinal fluid may thus contribute to the maintenance of chronic pain in these rats by reducing the endogenous inhibitory tone provided by opioid peptides and may be involved in the phenomenon of opioid insensitivity.

Animals↗
PubMed1999

Cholecystokinin/opioid interactions.

Cholecystokinin (CCK) acts as an anti-opioid peptide. The mechanisms of CCK-opioid interaction under normal and pathological conditions were examined with various techniques. Nerve injury induces upregulation of CCK mRNA and CCK2 receptors in sensory neurons. The involvement of CCK in spinal nociception in normal and axotomized rats was examined. The CCK2 receptor antagonist CI-988 did not reduce spinal hyperexcitability following repetitive C-fiber stimulation in normal or axotomized rats, suggesting that CCK is probably not released from injured primary afferents. With in vivo microdialysis intravenous (i.v.) or intrathecal (i.t.) morphine increased the extracellular level of CCK in the dorsal horn in a naloxone reversible manner. Morphine also released CCK after axotomy, but not during carrageenan-induced inflammation. In contrast, K(+)-stimulation failed to increase extracellular levels of CCK in axotomized rats, but did so in inflamed rats. Double-coloured immunofluorescence technique revealed partial co-localization between CCK-like immunoreactivity (LI) and mu-opioid receptor (MOR)-LI in superficial dorsal horn neurons. The presence of MOR in CCK containing neurons suggests a possible direct influence of opioids on CCK release in the spinal cord. Axotomy, but not inflammation, induced a moderate decrease in CCK- and MOR-LI in the dorsal horn. I.v. morphine further temporarily reduced CCK- and MOR-LIs in axotomized, but not in normal or inflamed, rats. While the effect of morphine on CCK-LI can be interpreted as the result of increased CCK release, the effect on MOR-LI may be related to changes in the microenvironment of the dorsal horn induced by nerve injury.

Animals↗
PubMed1999

Extracellular cholecystokinin levels in the rat spinal cord following chronic morphine exposure: an in vivo microdialysis study.

Conflicting results concerning the issue of whether or not chronic morphine exposure induces an increase in CCK biosynthesis have been found in many CNS sites, including the spinal cord, where CCK activity may contribute to the facilitation of the development of opiate tolerance. The present study was undertaken in order to monitor the extracellular level of CCK under spontaneous and stimulus-evoked release in the spinal cord dorsal horn of drug naive and morphine tolerant rats. Tolerance was induced by implantation of two morphine pellets (2x75 mg) which induced a stable morphine plasma concentration after 48 h post-implantation. The tail-flick test and naloxone precipitated withdrawal were used as indexes of tolerance and dependence to morphine. The effect of morphine-pellet implantation on basal and K+-induced release of CCK-like immunoreactivity (CCK-LI) in the rat dorsal horn were monitored with in vivo microdialysis 96 h after implantation of morphine or placebo pellets, when rats showed tolerance and dependence. Basal CCK levels were below the detection limit of the assay (0.6 pM) in both tolerant and normal animals. K+ (100 mM) in the perfusion medium induced a more than 3-fold increase of the extracellular level of CCK-LI in control animals, and a more than 4-fold increase on CCK-LI in morphine-pellet implanted animals. However, this difference was not significant. In addition, naloxone (2 mg/kg; i.v.), did not induce any change in the extracellular level of CCK in either group. The present study suggests that the modulatory interaction between CCK and opioids in the development of tolerance in the spinal cord may occur without necessarily increasing the extracellular level of CCK. Another possible explanation of the finding is that the microdialysis technique is not sensitive enough to detect differences in unstimulated CCK levels in normal and tolerant animals.

Analgesics, Opioid↗
PubMed1999

Measurement of cholecystokinin release in vivo in the rat spinal dorsal horn.

The microdialysis technique, used to monitor extracellular levels of transmitter substances in the central nervous system of laboratory animals as a reflection of transmitter release, is based on the ability of neurotransmitters to diffuse in the extracellular fluid from the site of release and to cross a semipermeable dialysis membrane. Even though the surgical procedure is not very complicated, the detection of released substances in the recovered dialysate may be difficult. Especially, the measurement of neuropeptide release is limited by the low extracellular concentration and of low recovery as compared to, for example, monoamines. Thus, for example, cholecystokinin (CCK), which is the most abundant neuropeptide in the central nervous system, is found at concentrations that are several orders of magnitude lower than those of classical transmitters. Therefore a highly sensitive detection method is of utmost importance. In the dorsal horn of the spinal cord CCK is found mainly in interneurons and in terminals of descending fibers. CCK seems to be involved in nociceptive transmission and CCK attenuates morphine-induced antinociception. We here describe in vivo microdialysis in the lumbar dorsal horn of the rat with subsequent quantification of the level of CCK-like immunoreactivity (-LI) by a highly sensitive radioimmunoassay.

Afferent Pathways↗
PubMed1998

Peripheral axotomy influences the in vivo release of cholecystokinin in the spinal cord dorsal horn-possible involvement of cholecystokinin-B receptors.

An increased expression of cholecystokinin (CCK) messenger RNA (mRNA) as well as CCK-B receptor mRNA in dorsal root ganglion (DRG) cells following peripheral axotomy has previously been demonstrated. In the present in vivo microdialysis study, the effect of unilateral sciatic nerve section on basal and potassium-induced release of CCK-like (CCK-LI) immunoreactivity in the rat dorsal horn was investigated. We also compared the effects of the CCK-B receptor antagonist CI988 on basal and potassium-stimulated CCK-LI release in intact animals and in chronically axotomized rats. Perfusion of the microdialysis probe with KCl (100 mM) induced a more than 6-fold increase of the extracellular level of CCK-LI in control animals. In contrast, following unilateral sciatic nerve section the same KCl stimulation failed to evoke a release of CCK-LI ipsilaterally. However, after systemic administration of CI988 (1 mg kg-1, i.v.), 100 mM KCl induced a significant increase of the extracellular CCK-LI level in axotomized rats, similar to that observed in control animals. In control animals no effect of CI988 on KCl-stimulated CCK-LI release could be detected. CI988 by itself had no influence on the extracellular CCK-LI level in either nerve injured or control animals. The present data suggest that axotomy reduces the release of CCK-like immunoreactivity in the spinal cord by a mechanism involving the CCK-B receptor binding site.

Animals↗
PubMed1998

Differential release of cholecystokinin by morphine in rat spinal cord.

The analgesic efficacy of opioids is reduced in neuropathic pain states and increased in inflammation. Since the neuropeptide cholecystokinin (CCK) plays a role in the modulation of opiate-induced analgesia, the morphine-mediated release of CCK in the spinal cord of rats was compared with in vivo microdialysis in normals and different pain models. The effect of systemic and intrathecal (i.t.) morphine on the extracellular level of CCK was analyzed in the spinal cord dorsal horn of halothane-anaesthetized normal rats as well as during peripheral neuropathy and inflammation. No difference was found in basal CCK level among groups. However, morphine significantly increased extracellular CCK concentration after both systemic and spinal application in intact as well as axotomized rats and this effect was naloxone-reversible in non-lesioned animals. Similar results were seen in axotomized rats. In contrast, morphine did not induce CCK release during carrageenan-induced inflammation. These data provide evidence that the ability of opiates to release CCK under different pain states may play a key role in their analgesic efficacy.

Analgesics, Opioid↗
PubMed1998

Sexual motivation promotes oxytocin secretion in male rats.

The present study examines plasma oxytocin levels in relation to performance of copulatory behavior in male rats. The animals were divided into three groups: A) home-cage controls, B) sexually naive and C) sexually experienced. Following 15 min of sexual interactions with a sexually proceptive female, brought into estrus by sequential injections of estradiol benzoate (12.5 micrograms animal-1, -48 h) and progesterone (0.5 mg animal-1, -6 h), the male rats were decapitated. Trunk blood was collected for preparation of plasma samples, and subsequent radioimmunoassay for oxytocin. Home-cage controls, not exposed to a sexually proceptive female, were decapitated at the same time as experimental animals. It was found that plasma oxytocin levels were significantly elevated in sexually naive rats following exposure to a sexually proceptive female, and that plasma oxytocin levels were highly correlated with intensity of copulatory performance in these animals. In addition, it was also found that plasma prolactin and glucose levels were increased, regardless of sexual experience, in comparison with home-cage controls. It is concluded that the emotional challenge, and the situation-specific demands for action, created by an encounter with a sexually proceptive female, are accompanied by an increased plasma concentration of oxytocin in sexually naive, but not sexually experienced, male rats.

Animals↗
PubMed1998

Steroid dependent effects of oxytocin on spontaneous motor activity in female rats.

In the present study, dose relationships for effects of oxytocin (OXY) on spontaneous motor activity in female rats were investigated. Ovariectomized (OVX) and cycling female Sprague-Dawley rats were given OXY 10-1000 microg/kg s.c. or saline, 10 min before registration of motor activity in an open-field arena. In the OVX rats, 100 microg/kg of OXY increased the activity in the center of the arena, whereas 1000 microg/kg decreased locomotor activity (LA). In the cycling rats, OXY 100-1000 microg/kg decreased LA during diestrus, while 1000 microg/kg also decreased LA during metestrus. The latter dose also reduced the exploratory behavior during estrus. In a second experiment, OVX rats were pretreated with estradiol benzoate (EB) and progesterone (P). When P levels were predominant, OXY 10-1000 microg/kg decreased LA. Oxytocin 10-100 microg/kg given after pretreatment with EB increased the activity in the center of the arena, whereas 1000 micro/kg given in the presence of both EB and P increased peripheral activity (PA). These results show that the effects of OXY on motor activity in female rats are modified by female sex steroid hormones.

Analysis of Variance↗
PubMed1998

Postnatal oxytocin injections cause sustained weight gain and increased nociceptive thresholds in male and female rats.

The aim of the present study was to investigate possible long-term effects of postnatally administered oxytocin on weight gain, gastrointestinal hormone levels, and nociceptive thresholds in rats. For this purpose, s.c. daily injections of oxytocin (1 mg/kg) or saline (NaCl, 0.9%) were given to male and female rat pups on d 10-14 after birth. The animals were killed at the age of 60 or 94 d. Treatment with oxytocin resulted in higher body weight in males, 60 d after birth, and in females from d 60 and throughout the rest of the experiment, compared with controls. The higher body weight was due to an increased weight gain in oxytocin-treated rats, compared with controls, which was most pronounced between 40 and 60 d after birth. Oxytocin-treated male rats had increased circulating levels of cholecystokinin, a tendency to increased plasma levels of insulin (p = 0.066), and relatively more adipose tissue in the thigh and interscapular region, compared with controls. At the age of 60 d, oxytocin-treated female and male rats had a prolonged withdrawal latency when measured in the tail-flick test, compared with controls. This study shows that oxytocin can induce long-lasting changes in weight gain, hormone levels, and nociceptive thresholds, when administered postnatally, in female and male rats.

Adipose Tissue↗
PubMed1997

Influences of fat and carbohydrate on postprandial sleepiness, mood, and hormones.

Paired studies were conducted in 18 healthy volunteers (9 men, 9 women) to investigate whether differences in mood and daytime sleepiness induced by high-fat-low-carbohydrate (CHO) and low-fat-high-CHO morning meals were associated with specific hormonal responses. Plasma insulin concentrations were significantly higher after low-fat-high-CHO meals, and cholecystokinin (CCK) concentrations were significantly higher after high-fat-low-CHO meals. Subjects tended to feel more sleepy and less awake 2-3 h after the high-fat-low-CHO meal, and ratings of fatigue were significantly greater 3 h after the high-fat-low-CHO meal than after the low-fat-high-CHO meal. The results of the present study are consistent with the hypothesis that there is an association between the lassitude experienced after a meal and the release of CCK.

Adult↗
PubMed1997

Development of a preferential relationship with the mother by the newborn lamb: importance of the sucking activity.

Lambs develop a preferential relationship with their mothers within 24 h after birth. In a first experiment, we attempted to determine whether neonatal sucking was a potent reinforcer in the establishment of this preference by temporarily covering the udders of ewes after parturition. Lambs were assigned to one of three treatments: they had free access to the udder (group 1) or were prevented from sucking either between birth and 6 h afterward (group 2) or between 12 and 18 h after birth (group 3). Measurements of cholecystokinin plasma levels at birth and at 6 and 18 h showed that all lambs ingested some colostrum when the udder was made accessible. When tested in a two-choice test situation at 24 h of age, lambs from group 1 spent significantly more time near their mothers than near the alien ewes, those from group 2 did not show any discrimination, and lambs from group 3 clearly preferred the alien ewes. At 2 days of age, lambs from groups 1 and 3 showed a strong preference for their mothers, whereas those from group 2 still displayed no preference. In a second experiment, we attempted to determine whether sucking also had a reinforcing value in the maintenance of this preference. Lambs were assigned to one of three treatments: they had free access to the udder (group 1) or were prevented from sucking for 6 h either at birth (group 2) or at the age of 3 days (group 3). Lambs from group 2 did not discriminate between their own and alien dams when tested at 24 h of age, unlike those of groups 1 and 3. When a second test was performed at 4 days of age, all the lambs showed a strong preference for their dams. We concluded that sucking has strong rewarding properties in the establishment of a preferential relationship with the mother by the lamb. On the other hand, the maintenance of this preference does not rely on sucking as strongly.

Animals↗
PubMed1997

Cholecystokinin receptors mediate the development of a preference for the mother by newly born lambs.

The aim of this study was to investigate the effect of selective cholecystokinin (CCK) antagonists on the development of a preference for the mother by newly born lambs. At birth lambs received an injection of the CCK-A antagonist devazepide (0.01 or 0.1 mg/kg), the CCK-B antagonist PD135158 (0.01 or 0.1 mg/kg), or saline for the controls (1 ml/kg). No major side effects were observed in the first 4 postnatal hours except that lambs receiving PD135158 displayed more exploratory behavior towards the maternal body than lambs from the other groups. When tested in a 2-choice test situation at 24 hr of age, lambs treated with PD135158 or saline spent significantly more time near their dams than near the alien ewes, whereas lambs treated with devazepide did not show any discrimination. The effect of devazepide persisted at 48 hr of age. The use of a CCK-A antagonist, but not a CCK-B antagonist, was concluded to prevent the formation of a preferential relationship between the lamb and its mother, most probably by impairing neonatal learning.

Animals↗
PubMed1996

Oxytocin increases nociceptive thresholds in a long-term perspective in female and male rats.

Oxytocin (0.1 and 1.0 mg/kg s.c.) given to male rats during 5 days, increased tail-flick latency when measured 1 (P < 0.05) and 7 days (0.1 mg/kg, P < 0.05; 1.0 mg/kg, P < 0.01) after the last injection. The effect was gone 2 weeks after the end of the treatment. If an additional injection of oxytocin was given 10 days after a previous 5 day treatment period, the significant difference persisted after 3 weeks (P < 0.05). Tail-flick latency was significantly delayed also in oxytocin-treated females when measured 1 week after the treatment period (P < 0.05). Naloxone, but not an oxytocin antagonist, temporarily antagonised the oxytocin induced delay in withdrawal latency. This indicates that oxytocin may act by increasing the activity of opioid mechanisms.

Animals↗
PubMed1996

Effects of 5-HT agonists, selective for different receptor subtypes, on oxytocin, CCK, gastrin and somatostatin plasma levels in the rat.

Adult male Sprague-Dawley rats were administered the 5-HT subtype selective receptor agonists 8-OH-DPAT (0.5-2.0 mg/kg), buspirone (2-8 mg/kg) (5-HT1A), TFMPP (0.125-2.0 mg/kg) (5-HT1B), DOI (0.125-2.0 mg/kg) (5-HT2A) and m-CPBG (1.25-20.0 mg/kg) (5-HT3), subcutaneously. Oxytocin, cholecystokinin (CCK), somatostatin and gastrin plasma levels were determined by standard RIA techniques 30 and 120 min after injection of the respective 5-HT receptor agonist. It was found that the 5-HT1A and the 5-HT2A/C, but not the 5-HT2B or the 5-HT3 receptor agonists produced an increase in plasma oxytocin levels and these effects were, at least partially, antagonized by the corresponding subtype selective antagonists (-)pindolol (2 mg/kg) and ritanserin (2 mg/kg), respectively, administered 10 min before 8-OH-DPAT (0.5 mg/kg) or DOI (0.5 mg/kg). The maximal response to the 5-HT1A receptor agonists (approx. 120 nmol/l) was from 8 to 5 times the maximal response to the 5-HT2A C receptor agonist. In addition, 8-OH-DPAT and DOI caused a decrease in plasma CCK levels, whereas the 5-HT1B receptor agonist TFMPP gave rise to an increase in plasma CCK levels. There were no statistically significant effects by any of the 5-HT receptor agonists on plasma somatostatin or gastrin levels under the present conditions. It is suggested that the clinical effects of new anxiolytic 5-HT1A receptor agonists, such as buspirone, to an extent may be mediated via an increased release of oxytocin.

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

Stroking of the abdomen causes decreased locomotor activity in conscious male rats.

The specific aim of the present study was to determine if stroking in conscious rats can influence spontaneous locomotor behavior in an open-field arena. For this purpose, conscious rats were held across the scapula and the ventral side of the abdomen was stroked at a pressure of 100-150 mm H2O and at a speed of approximately 20 cm/s. The stimulation frequency was approximately 40 strokes/min and the duration 2, 5, and 10 min. Animals held for 10 min served as controls. There was a significant decrease in rearing and locomotion and a significant increase in peripheral activity in the open-field arena after the treatment. Maximal effects were obtained after 5 min of stroking. These effects were consistent with a stroking-induced sedative effect similar to that seen in this open-field arena model following neuroleptics or large doses of oxytocin.

Animals↗
PubMed1996

Oxytocin causes a long-term decrease of blood pressure in female and male rats.

The aim of the present study was to investigate the long-term effects of oxytocin (OXY) on blood pressure (BP) and heart rate (HR) in conscious female and male rats. For this purpose, subcutaneous (SC) (0.01, 0.1, and 1 mg/kg) or intracerebroventricular (ICV) (1 microgram/kg) injections of OXY were given during 5-day periods. BP and HR were measured daily. A significant decrease in BP, without affecting HR, compared to saline-treated controls was seen in response to 0.1 (males: p < 0.01, females: p < 0.001) and 1 mg/kg (p < 0.001) of OXY given SC. BP gradually returned to preexperimental levels within 10 days after the last injection in male rats but, in females, the significant lowering of BP remained unchanged during this period. Also OXY ICV (1 microgram/kg) decreased BP (p < 0.05 after one day, p < 0.001 after 5 days of injections). This effect was still present 8 days after the last injection (p < 0.05). These results indicate that OXY may induce a long-term lowering of BP.

Animals↗