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Biomedical subjects

F C Colpaert

Publications and source records attributed to F C Colpaert.

At least 127 records · Page 7Linked to original sources
PubMed1986

Epidural and intravenous sufentanil in the rat: analgesia, opiate receptor binding, and drug concentrations in plasma and brain.

Doses of sufentanil (i.e., 0.01, 0.04, 0.16, 0.63, 2.5, 10, and 40 micrograms/rat) were injected either into the lumbar epidural space or intravenously in rats weighing +/- 250 g, and in vivo pharmacologic activities (i.e., prolongation of latency to tail withdrawal in response to noxious heat, blockade of cornea and pinna reflexes, increase of skeletal muscle tone), ex vivo mu-opiate receptor binding (i.e., displacement of specific 3H-sufentanil binding in thalamus, striatum, hippocampus, cortex, mamillary body-medulla oblongata segment, medulla oblongata, and in cervical, thoracic, and lumbar spinal cord), and drug concentrations in plasma, brain, cortex, and cerebellum, were determined. An ED50 dose of intravenous sufentanil of 0.075 micrograms/rat produced analgesia. CNS-mediated in vivo side effects (i.e., blockade of pinna and cornea reflexes, muscle rigidity) were apparent at 6-28 times higher doses. Epidural sufentanil also produced analgesia at an ED50 dose of 0.08 micrograms/rat, but CNS-mediated side effects occurred only at 35 to 76 times higher doses. This greater in vivo selectivity of epidural sufentanil in producing analgesia was consistent with ex vivo binding data that showed that in most areas of brain, but not in spinal cord, more mu-opiate binding occurs with intravenous than with epidural sufentanil. The two routes nonetheless differed by no more than a factor of approximately two in producing detectable levels of sufentanil both in plasma and in brain tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗
PubMed1986

A model of chronic pain in the rat: response of multiple opioid systems to adjuvant-induced arthritis.

Chronic arthritic pain was induced by intradermally inoculating rats at the tail-base with Mycobacterium butyricum, which results in swelling, inflammation, and hyperalgesia of the joints. These symptoms peak at 3 weeks after inoculation and disappear by 10 weeks. The following changes were seen at 3 weeks. Immunoreactive dynorphin (ir-Dyn) and ir-alpha-neo-endorphin (alpha-NE) manifested comparable patterns of change. Their levels were increased in the anterior, but not neurointermediate, pituitary. The thalamus showed a rise in ir-Dyn and ir-alpha-NE, but no alterations were seen in other brain regions. In each case, cervical, thoracic, and lumbosacral sections of the spinal cord showed a rise in ir-Dyn and ir-alpha-NE: This was most pronounced in the lumbosacral region, where the magnitude of these shifts correlated with the intensity of arthritic symptoms. In addition, a moderate elevation in ir-methionine-enkephalin (ME) was seen in lumbosacral spinal cord. In brain, ir was not changed. The level of ir-beta-endorphin (beta-EP) was elevated both in the plasma and the anterior, but not the neurointermediate, pituitary. In addition, the content of messenger RNA encoding the beta-EP precursor, proopiomelanocortin (POMC), was enhanced in the anterior lobe. Thus, there was a selective activation of synthesis of beta-EP in, and its secretion from, the anterior lobe. In no brain tissue did levels of ir-beta-EP change. At 10 weeks postinoculation, the above changes were no longer apparent, indicating their reversibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Respiratory effects of morphine in awake unrestrained rats.

This report describes a systematic analysis of opiate drug effects on ventilation and its components tidal volume and frequency in intact, awake and unrestrained rats. A whole-body plethysmographic method was used to measure these parameters of respiration while animals breathed air or various concentrations of CO2 in air. Subcutaneous doses of morphine lower than 40 mg/kg exerted little or no apparent effect in rats breathing air; in rats breathing 4 to 8% of CO2 these doses of morphine also failed to depress any of the ventilatory parameters below the level of saline controls breathing air. Doses (0.16 to 160 mg/kg) of morphine blunted the frequency response to CO2 in a biphasic manner. The effects of morphine on tidal volume consisted of a slight increase at 0.16 and 0.63 mg/kg, a dose-dependent decrease at 2.5 to 40 mg/kg and a paradoxical rise at 160 mg/kg. These complex effects of morphine on tidal volume and frequency resulted in a simple sigmoid depression of minute volume. The slope of this sigmoid dose-response curve varied with the inspirate; it increased as the concentration of CO2 was higher. Naloxone antagonized the frequency depression produced by 40 mg/kg of morphine in a dose-dependent manner at doses ranging from 0.01 to 0.16 mg/kg, but frequency decreased again at 0.63 mg/kg. The effects of naloxone on the tidal volume depression consisted of a paradoxical further decrease at 0.01 mg/kg, a dose-dependent antagonism of depression at 0.04 to 0.16 mg/kg and a stimulation above the normal control level at 0.63 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Spinal cord dynorphin may modulate nociception via a kappa-opioid receptor in chronic arthritic rats.

Inoculation of rats with Mycobacterium butyricum produced an arthritis of the limbs which revealed an enhanced sensitivity to noxious mechanical pressure (hyperalgesia). Arthritic rats displayed a pronounced rise in immunoreactive dynorphin in lumbo-sacral spinal cord which correlated both with the intensity and time-course of this hyperalgesia. MR-2266, a relatively preferential antagonist at the chi-opioid receptor (at which dynorphin is considered to act) potentiated this hyperalgesia. In contrast, MR 2267 (its inactive stereo-isomer) was ineffective. Further, naloxone (a weak chi-antagonist), and ICI 154,129 (a preferential delta-antagonist) were, in each case, inactive. The data demonstrate a pronounced response of spinal dynorphin to chronic arthritic pain in the rat. In addition, they raise the possibility of a function of spinal DYN, via a chi-receptor, in the modulation of chronic arthritic pain.

Animals↗
PubMed1985

Chronic arthritis in the rat: differential changes in discrete brain pools of vasopressin as compared to oxytocin.

Rats inoculated in the tail-base with killed Mycobacterium butyricum developed an arthritic swelling and inflammation of the limbs accompanied by a hyperalgesia to noxious pressure applied thereto. These changes were maximal at 3 weeks and had subsided by 10 weeks post-inoculation. At 3 weeks, arthritic rats manifested an elevation in levels of immunoreactive (ir)-vasopressin (VP) but not ir-oxytocin (OT) in the midbrain. In contrast, ir-OT was increased in the medulla-pons while ir-VP was unaltered therein. These changes had disappeared by 10 weeks. No other brain region displayed changes. Thus, chronic arthritis is associated with selective and reversible effects upon discrete brain pools of ir-VP and ir-OT. The data clearly demonstrate that pools of ir-VP and ir-OT can be modulated independently of each other in particular brain tissues. Whether the changes are produced by, or reflect a functional response to, the pain rather than other characteristic of the arthritis, remains to be determined.

Animals↗
PubMed1985

Behavioral and 5-HT antagonist effects of ritanserin: a pure and selective antagonist of LSD discrimination in rat.

The newly synthesized compound and putative 5-HT2 antagonist ritanserin, but not the structurally related compound R 56413, resembles pirenperone in that it acts as a pure antagonist in an LSD-saline drug discrimination assay in the rat. Ritanserin exceeded pirenperone in terms of behavioral specificity; the lowest effective dose of ritanserin in antagonizing LSD was one order of magnitude higher than that of pirenperone, but the compound depressed rate of operant responding only at doses that were about 1000-fold higher than those at which pirenperone was effective. Ritanserin exerted effects in an open field test which were reminiscent of anxiolytic drug activity in the rat; its effects were greater than those of pirenperone, R 56413 and the benzodiazepines chlordiazepoxide and diazepam. The results of experiments on antagonism of 5-HT-induced hypothermia and of the 5-HTP-induced head-twitch response fail to support the possibility that the putative anxiolytic effects of ritanserin in the rat can be ascribed simply to a pharmacologically defined action at 5-HT receptors.

5-Hydroxytryptophan↗
PubMed1985

Chronic pain in the rat: selective alterations in CNS and pituitary pools of dynorphin as compared to vasopressin.

Inoculation of rats at the tail-base with Mycobacterium led to arthritic swelling and inflammation of all four limbs. Immunoreactive (ir)-dynorphin (DYN) increased in anterior but not neurointermediate pituitary. In the brain, only thalamus showed a rise and, in spinal cord, a large elevation was seen. Ir-vasopressin (VP) was not affected in these tissues but increased in midbrain. These effects might reflect a role of DYN in the control of chronic pain. In addition, they support a differential modulation of DYN as compared to VP extrinsic to the hypothalamic-neurohypophyseal axis.

Animals↗
PubMed1985

Discriminative stimulus properties of xylazine in rat: discriminability and effects of putative alpha-2 adrenoceptor agonists and antagonists.

In a first experiment, rats were trained initially to discriminate i.p. injections of 2.5 mg/kg of xylazine from saline in a two-lever, food-reinforced, fixed-ratio 10 drug discrimination procedure. The animals were then retrained on progressively lower doses of the training drug. The stimulus generalization gradient of xylazine was established each time the animals had reached criterion on successive training doses; the criterion required that lever selection be appropriate to the saline or xylazine injection on 10 consecutive sessions. The findings indicate the lowest xylazine training dose at which individual rats can reach criterion to range from 2.5 to less than or equal to 0.31 mg/kg; the median lowest discriminable dose was 0.89 mg/kg. The distribution of lowest discriminable dose accommodated a Gaussian shape. The slope of the xylazine gradient did not in a systematic manner vary as a function of training dose, and the ED50 value of xylazine was an almost constant fraction of training dose (1:2.0) at training doses ranging from 2.5 to 0.63 mg/kg. A second experiment examined the xylazine-like agonist and the xylazine-antagonist effects of clonidine, yohimbine, piperoxan and idazoxan in rats discriminating xylazine from saline at a training dose of 2.5 mg/kg. Clonidine produced generalization in all animals and antagonized the xylazine stimulus in one. Idazoxan produced near complete antagonism, and was generalized in one animal. Yohimbine and piperoxan produced magnitudes of agonist and antagonist effects that were intermediate between those of clonidine and idazoxan. Lisuride and d-lysergic acid diethylamide produced up to 71 and 29% generalization, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1984

A possible alpha 2-adrenergic component in the in vivo activity of pirenperone.

The study used the loss of the righting reflex in response to the alpha 2-agonist xylazine in an in vivo rat assay to determine possible effects of the LSD antagonist pirenperone at alpha 2-adrenoceptors. Pirenperone antagonized the response and was more potent (ED50: 0.32 mg/kg) than yohimbine (1.25 mg/kg) and piperoxan (3.30 mg/kg). The data suggest that pirenperone may act at alpha 2-adrenoceptors in vivo.

Animals↗
PubMed1984

Cross generalization with LSD and yohimbine in the rat.

Rats trained to discriminate intraperitoneal injections of 0.16 mg/kg LSD from saline injections were found to show stimulus generalization with 0.31-5 mg/kg of yohimbine. Partial generalization also occurred with clonidine and xylazine. Rats discriminating intraperitoneal injections of 5 mg/kg of yohimbine from saline generalized LSD at doses of 0.08-0.63 mg/kg. The data establish an equivalence between LSD and yohimbine as to discriminative effects in rats. This equivalence is consistent with LSD and yohimbine producing at least partly similar subjective effects in humans.

Animals↗
PubMed1984

Respiratory effects of intrathecal capsaicin in arthritic and non-arthritic rats.

The study determined the effects of intrathecal injection of 50 micrograms of capsaicin on respiration in rats with adjuvant arthritis as well as in control animals. Whole body plethysmographic measurements of steady-state frequency, tidal volume, and minute volume of respiration were made 3 hours and for up to 11 days after intrathecal injection. Capsaicin increased minute volume within 3 hours of its intrathecal injection in control animals. Intrathecal capsaicin also reduced the respiratory response to adjuvant arthritis in the experimental animals; the latter effect was apparent 11 days after injection. This biphasic pattern of capsaicin effects is consistent with a possible role of substance P in the chronic pain which is presumably associated with adjuvant arthritis in the rat.

Animals↗
PubMed1984

Agonist and antagonist effects of prototype opiate drugs in rats discriminating fentanyl from saline: characteristics of partial generalization.

The experiments reported here characterized the partial generalizations that prototype opiate drugs may produce in rats that are trained to discriminate 0.04 mg/kg of fentanyl from saline. Cyclazocine, nalorphine, ketocyclazocine and N-allylnormetazocine produced partial generalization with fentanyl; the same compounds also partially antagonized fentanyl. The fentanyl-like and the fentanyl-antagonist effects of these compounds occurred within similar ranges of dose. An orderly incompatibility was apparent between the agonist and antagonist effects produced by each drug; cyclazocine, for example, was unlikely to antagonize fentanyl in animals in which it produced generalization, whereas it did antagonize fentanyl in animals in which it produced no generalization. Cyclazocine, nalorphine, N-allylnormetazocine and naloxone produced either fentanyl-like or fentanyl-antagonist effects in all animals tested. A reliable relationship was apparent among the agonist and antagonist effects of different opiate drugs; rats that generalized cyclazocine also were likely to generalize nalorphine and ketocyclazocine and were relatively less responsive to cyclazocine, nalorphine, N-allylnormetazocine and naloxone as antagonists of fentanyl. The results point to the importance of a number of new methods in the analysis of drug discrimination data. Among these are the analysis of individual generalization data and the examination of agonist and antagonist effects of test drugs in the same animals. A parsimonious molecular interpretation of the data can be offered by assuming that morphine, ketocyclazocine, cyclazocine, nalorphine, N-allylnormetazocine and naloxone have affinity for, but differ in activity at, an opiate receptor where fentanyl acts to produce discriminative effects.

Animals↗
PubMed1983

Time course of the ventilatory response to adjuvant arthritis in the rat.

The present study determined the time course of the ventilatory response to adjuvant arthritis in the rat. It was found that the minute ventilation of arthritic rats reliably exceeded that of control animals during a period of about 4 weeks. The ventilatory response had its onset during the 2nd week after inoculation of Mycobacterium butyricum in the tail base, peaked on day 21, and was statistically reliable up to the 35th day. A smaller difference persisted throughout the further six weeks of the study, which covered 77 days in all. The changes in minute ventilation appeared to be closely time-locked with the changes in body weight and paw diameter which are characteristic of rats with adjuvant arthritis. The peak minute ventilation of individual animals also correlated in a significant manner with changes in weight and in paw diameter. The data are consistent with an earlier attempt to characterize the time course of the chronic pain which is presumably associated with adjuvant arthritis in the rat; minute ventilation is discussed as a possible measure of this putative pain.

Animals↗
PubMed1983

Effects of capsaicin on inflammation and on the substance P content of nervous tissues in rats with adjuvant arthritis.

Capsaicin (20-80 mg/kg, s.c.) reduced the inflammatory response to inoculation with Mycobacterium butyricum in the rat. The effect was apparent within 24 h, was partial, persisted for well over 20 days, and occurred irrespective of whether capsaicin was administered before or after the onset of inflammation, or at the time when the pathology reached peak. Capsaicin also attenuated the increase in substance P content in sciatic nerve, saphenous nerve, dorsal root ganglia, dorsal roots, and dorsal spinal cord (L4, L5) which occurs in rats with adjuvant arthritis. The data are consistent with a possible role of substance P in the peripheral manifestations of adjuvant arthritis.

Animals↗
PubMed1983

Ventilatory response to adjuvant arthritis in the rat.

This study examined ventilation in rats with arthritis induced by Mycobacterium butyricum. It was found that, 19 days after inoculation, the minute ventilation of arthritic rats breathing air was about two-fold higher than that of control animals. This increase resulted from an increase both in respiratory frequency and in tidal volume. Air-CO2 mixtures continued to stimulate ventilation in arthritic rats, and the minute ventilation of these animals on breathing 5 or 7% CO2 exceeded that of controls. The results are consistent with the hypothesis that arthritic rats hyperventilate and contribute to the validation of adjuvant arthritis as an animal model of chronic pain.

Animals↗
PubMed1983

The head-twitch response to intraperitoneal injection of 5-hydroxytryptophan in the rat: antagonist effects of purported 5-hydroxytryptamine antagonists and of pirenperone, an LSD antagonist.

The putative 5-hydroxytryptamine (5-HT) antagonists 2-bromo-LSD, cinanserin, cyproheptadine, pizotifen, methysergide, metitepine, mianserin and metergoline were found to reduce the frequency of the head-twitch response induced by intraperitoneal injections of 320 mg/kg of 5-hydroxytryptophan (5-HTP) in the rat. The antagonist dose-effect curve of these agents was biphasic. It consisted of an initial, steep, phase and a subsequent, shallower, phase. Analysis of the data by means of quantitative and quantal methods yielded different rank orders of potency of antagonist drugs. Only pirenperone, a drug identified earlier as a pure antagonist, produced a simple, monophasic dose-effect curve in antagonizing the effects of 5-HTP. The antagonist effects of pirenperone, and the first phase of the curve of the putative 5-HT antagonists, may reflect antagonist activity at 5-HT2 receptors. The data are consistent with earlier behavioural evidence that the putative 5-HT antagonists act complexly as mixed agonist-antagonists; only pirenperone exerted behavioural effects that suggest it to be a pure antagonist.

5-Hydroxytryptophan↗
PubMed1983

A characterization of LSD-antagonist effects of pirenperone in the rat.

Rats were trained to discriminate between intraperitoneal injections of 0.16 mg/kg of d-lysergic acid diethylamide (d-LSD) and injections of saline in the two-bar (FR 10) food-reinforced drug discrimination procedure. The gradient for responses to LSD was established following pretreatment with saline or one of five doses of pirenperone. It was found that pretreatment with pirenperone caused a parallel shift to the right of the dose-effect curve of LSD. The magnitude of this shift was related to the dose of pirenperone, 0.006 mg/kg of the drug causing a 2-fold shift. A direct linear plot revealed that the curve fitting the data points passed through the origin, but that it was curvilinear rather than linear. The data did not, therefore, accommodate the requirements for reversible, competitive interaction. This finding is discussed in terms of the mixed agonist/antagonist activity of LSD that may occur at binding sites for 5-HT1 and 5-HT2 in the rat brain.

Animals↗