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Biomedical subjects

A Laferrière

Publications and source records attributed to A Laferrière.

At least 19 recordsLinked to original sources
PubMed2001

Effects of age and clustered hypoxia on [(125)I] substance P binding to neurotachykinin-1 receptors in brainstem of developing swine.

This work focused on the postnatal development of substance P-bound neurotachykinin-1 (NK-1) receptors in the porcine brainstem using 2-3-, 6-11-, 16-18-, and 21-28-day-old piglets versus adult, and on alterations in these receptors after single and six-daily repeated clustered hypoxia using 6-11- and 21-28-day-old piglets. NK-1 receptor localization and densities were determined by quantitative autoradiography using mono-iodinated Bolton-Hunter substance P ([(125)I]BHSP). Slide-mounted brainstem sections, incubated in [(125)I]BHSP and then exposed to film, have shown [(125)I]BHSP binding throughout many brainstem nuclei and tracts, including the ambigual/periambigual (nAmb), dorsal motor vagal (dmnv), gigantocellular (nGC), hypoglossal (nHyp), medial parabrachial (nPBM), lateral reticular (nRL), raphe magnus (nRMg), raphe obscurus (nROb) and solitary tract (nTS) nuclei. NK-1 receptor densities decreased with age. As compared to normoxia, NK-1 receptor densities increased significantly after the six-daily hypoxia protocol in nAmb, dmnv, nHyp, nRL, nRMg, nROb, and nTS of both the young and older age groups. This increase may represent receptor upregulation as an adaptation to repeated hypoxia.

Age Factors↗
PubMed2000

Repeated prenatal cocaine increases met-enkephalin immunoreactivity in respiratory-related medulla of developing swine.

Repeated prenatal exposure to cocaine is associated with attenuated respiratory and arousal responses in infants and piglets. As the normal development of these functions is influenced by medullary opioid systems, the present study explored the possible contribution of the opioid systems to the attenuation induced by cocaine. Methionine-enkephalin (met-enkephalin), an endogenous opioid peptide, was delineated by immunocytochemistry in respiratory- and arousal-related medullary regions of relatively immature (6-7-day-old) and more mature piglets (20-21-day-old). The animals were either unexposed, or exposed prenatally to 2 mg/kg cocaine four times daily administered to the pregnant sows intravenously throughout the last third of gestation. At control, met-enkephalin was found in the neurons, fibers and terminals of the respiratory- and arousal-related medullary regions throughout the age range studied. Prenatal cocaine exposure increased met-enkephalin immunoreactivity in the respiratory-related hypoglossal and solitary tract nuclei of both age groups. These findings support a modulatory role of met-enkephalin in the normal development of respiratory control, and an involvement of this peptide in the attenuation of respiration by repeated prenatal exposure to cocaine.

Animals↗
PubMed1999

Mu- and delta-opioid receptor densities in respiratory-related brainstem regions of neonatal swine.

The piglet displays similar postnatal development in respiration and sleep-wake behavior to the human. To shed light on the possible influence of opioid systems on these functions, this study assessed the density of mu- and delta-opioid receptors in brainstems of 2-3 and 5-7 (young), 14-17 (intermediate) and 20-21 (older) day-old piglets, using quantitative autoradiography. Serial 10 microns sections from fresh-frozen brains were incubated with either mu-(125I-DAGO) or delta-(125I-DPDPE) opioid ligands. The binding characteristics of each receptor remained unchanged over the age-range studied. delta-opioid receptor density was minimal in the young piglets, and increased over the age-range studied in all brainstem regions. mu-opioid receptor density exceeded delta-opioid density in all brainstem regions in young and older piglets, and remained unchanged with age. We conclude that, as in other species, the development of delta-opioid receptors in swine lags behind that of mu-opioid receptors, and that the distribution of each in the piglet's brainstem is distinct. The present findings help explain the changing influence of the mu- and delta-opioid systems on breating and state during postnatal development.

Analgesics↗
PubMed1998

Prenatal cocaine alters normoxic sleep-wake and diaphragmatic EMG patterns in piglets.

This study assessed in piglets the effects of prenatal cocaine administration on sleep-wake states (SWS) and respiratory parameters, utilizing diaphragmatic electromyogram (EMGdi) recordings during normoxia before and after hypoxia (0.10 F(I,O2), 10 min). We asked whether the respiratory effects were linked to a specific SWS, and whether there was a difference in respiratory measures between the two normoxic conditions. Unsedated, chronically instrumented 3-9- or 21-31-day-old piglets, representing distinct stages in developmental respiratory control, were used. In pre-hypoxic normoxia, prenatal cocaine enhanced sleep at the expense of wakefulness and increased EMGdi amplitude, slope, and area in both age groups regardless of SWS; after the hypoxia, the respiratory findings persisted in the young group, but disappeared in the older group [corrected]. In the young group and regardless of SWS, interbreath interval (ttot) and expiratory duration (ttot - tEMGdi[duration of EMGdi]) were shorter in the cocaine-exposed than in the unexposed piglets, and ttot, tEMGdi, and (ttot - tEMGdi) decreased from pre- to post-hypoxic normoxia. In the older group, ttot and (ttot - tEMGdi) differed among SWS, but were unaffected by drug treatment; tEMGdi was higher with cocaine exposure in pre-, but not in post-hypoxic normoxia, and two-thirds of the EMGdi measurements during post-hypoxic normoxia exhibited a similar magnitude in the drug-treated and untreated groups regardless of SWS. We conclude that 1) prenatal cocaine alters both SWS and EMGdi, but the EMGdi effects are independent of SWS; and 2) the similar EMGdi patterns in the older group after hypoxia, regardless of drug treatment, suggest that hypoxia and chronic prenatal cocaine might alter EMGdi by similar mechanisms.

Age Factors↗
PubMed1997

Curtailed respiration by repeated vs. isolated hypoxia in maturing piglets is unrelated to NTS ME or SP levels.

In early development, respiratory disorders can produce recurring hypoxic episodes during sleep. To examine possible effects of daily repeated vs. isolated hypoxic hypoxia, cardiorespiratory functions and central, respiratory-related neuromodulator levels in 21- to 32-day-old, chronically instrumented, unsedated piglets were compared between a fifth sequential daily hypoxia and an isolated hypoxia (10% O2-90% N2 for 30 min). Diaphragmatic electromyographic activity, heart rate and arterial pressure, and pH and gas tensions were measured. In vivo microdialysis, via chronically implanted guides, served to sample interstitial substance P (SP) and methionine-enkephalin (ME) at the level of the respiratory-related nucleus tractus solitarii (NTS). Compared with an isolated hypoxia, repeated hypoxia resulted in 1) lower respiratory frequency (f), ventilation equivalent, and arterial pH, higher arterial PO2 during hypoxia, and lower f in recovery from hypoxia; and 2) increased SP concentrations but no change in ME concentrations. We conclude that, in these maturing swine, repeated vs. isolated hypoxic exposure curtails respiratory responses to hypoxia by a mechanism(s) unrelated to SP or ME levels at the NTS.

Aging↗
PubMed1997

Repeated microdialysis from the nucleus tractus solitarii of chronically instrumented, unsedated piglets.

Normal development of respiratory rhythm and control, and perturbations thereof, likely relate to neuromodulators in brainstem regions. To assess the feasibility of repeated neurochemical sampling by in vivo microdialysis from the respiratory-related nucleus tractus solitarii (NTS) during development. 19-24 day-old piglets (n = 7) were implanted under anesthesia with chronic microdialysis guides near NTS around obex. Unsedated piglets then underwent in vivo microdialysis twice, 3 days apart, through probes inserted acutely via the guides to abut against the NTS. The probe tips, surrounded by normal neurons and only diffuse gliosis, either intersected, or were within < or = 300 microns from the NTS. Thirty-min microdialysates were collected for 120 min in normoxia, HPLC-fractionated, and assayed for substance-P (SP), a respiratory excitatory neuropeptide. SP levels stabilized within 90 min from probe placement, and did not differ between the 2 experimental days. Thus, repeated in vivo microdialysis from NTS of conscious piglets is feasible, and can illuminate respiratory-related normal and pathological neurochemical processes during development.

Animals↗
PubMed1995

Cardiorespiratory and sleep-wake behavior in developing swine: kappa-opioid influence.

Effects of specific kappa-opioid antagonism with norbinaltorphimine (NorBNI) on sleep-wake state, blood pressure and heart rate, and on diaphragmatic and posterior cricoarytenoid electromyographic activities were assessed in 3 to 13 and 23 to 33 day-old, chronically instrumented, unanesthetized piglets. Preliminary experiments established the pharmacodynamics and dose-response for NorBNI. In the main study, each piglet was studied twice daily, once before and once after 3.7 mg kg-1 NorBNI iv, for up to five consecutive days. During each study session, piglets underwent 10 min trials with 21% O2 in 79% N2 followed by 10% O2 in 90% N2 while lying in a sling within a plexiglass box. Sleep-wake distribution and cardiorespiratory functions matured with age. NorBNI produced a modest increase of arterial pressure and heart rate in the older group only, and altered neither state nor respiration at either age. These results suggest that, in the developing piglet model, the kappa-opioid system influences neither breathing nor state, but modulates cardiovascular regulation to a modest degree and later in ontogeny.

Aging↗
PubMed1995

Microdialyzed adenosine in nucleus tractus solitarii and ventilatory response to hypoxia in piglets.

Levels of adenosine, inosine, and hypoxanthine from the interstitial space at the nucleus tractus solitarii were measured by microdialysis in eight 20- to 25-day-old anesthetized spontaneously breathing piglets. Microdialyzed samples were collected every 30 min for 2 h after the insertion of the probe to ensure stability of purine levels and then during 30 min each of normoxia, hypoxia (10% O2-90% N2), and normoxia. The purines were separated by high-pressure liquid chromatography with ultraviolet detection and quantified at 254-nm wavelength. Tidal volume, breathing frequency, minute ventilation, mean arterial blood pressure, pH, and gas tensions were measured. Compared with control, adenosine levels during hypoxia increased by 40.7 +/- 5.5% and then tended to decline during the recovery from hypoxia, but the levels remained higher than in control. Ventilatory measures exhibited a modest biphasic pattern during hypoxia and resumed control values by 10 min after the removal of the hypoxia. The increased adenosine release during hypoxia provides additional evidence for the possible participation of adenosine in the central suppression of breathing during hypoxia.

Adenosine↗
PubMed1995

Chronic prenatal cocaine retards maturation of state and of respiratory patterns in swine.

This study assessed effects of prolonged prenatal cocaine exposure on respiratory pattern and sleep-wake states in a postnatal porcine model. Yucatan miniature sows received 2 mg/kg cocaine intravenously four times daily during 0.66-1.0 gestation. At birth, cocaine-exposed litters were fostered to unexposed paired sows and their litters. Chronically instrumented piglets were studied at 3-9 (young) and 21-31 days (older). Sleep-wake states were determined from electrocorticogram, eye movements, submental electromyogram, and behavior, and respiratory patterns were determined from diaphragmatic and posterior cricoarytenoid electromyograms (EMGdi and EMGpca, respectively). Under baseline conditions, prenatal cocaine 1) increased the number of apneas expressed by silence of EMGdi or EMGpca and prolonged the duration of EMGpca-related apneas at both ages; 2) increased the number of periodic breathing episodes at both ages; 3) increased percent time of active sleep and decreased that of wakefulness at both ages; and 4) increased time in quiet sleep in the older animals, producing in them a sleep-wake distribution similar to that of the young neonates. Whereas the findings in the youngest piglets may have been influenced by persistent systemic cocaine, those in the older preexposed piglets, devoid of systemic cocaine, imply that chronic prenatal cocaine retards the postnatal maturation of state and respiratory pattern.

Animals↗
PubMed1995

Prenatal cocaine alters diaphragmatic EMG responses to hypoxia in developing swine.

To distinguish pure effects of prenatal cocaine exposure on respiratory control from confounding factors inherent to drug abuse, a porcine model was established. Cocaine was administered at 2 mg/kg 4 times daily during 0.66-1.0 gestation to 5 paired sows. At birth, cocaine-exposed piglets were fostered to the unexposed paired sows and their litters. Respiratory measures were obtained from diaphragmatic electromyographic activity (EMGDI) of 3 to 9 (young) and 21 to 31 (older) day-old, chronically instrumented piglets during 10 min each of normoxia and hypoxia (10% O2 in 90% N2), and compared between cocaine-exposed and unexposed animals. Arterial pH and gas tensions in hypoxia were not altered by cocaine. In the young neonates, only during hypoxia, cocaine preexposure produced a transient elevation of the peak and initial slope of the integrated EMGDI envelope, but did not affect respiratory timing, provided no extensive periodic breathing or apnea had occurred. In the older animals, during hypoxia only, cocaine preexposure increased the peak and initial slope of EMGDI envelope while decreasing summed EMGDI activity, EMGDI duration and Ttot toward levels seen in the young unexposed neonates. These findings suggest that prenatal exposure to cocaine retards the normal maturation of respiratory EMG responses to hypoxia.

Animals↗
PubMed1994

Age-related electrocorticographic and respiratory adaptation to repeated hypoxia.

Severe hypoxia is known to produce depression in electrical brain activity and perturbation of respiratory pattern. In piglets undergoing chronic recording of brain and respiratory muscle activities, a depressed electrocorticogram (ECoG) was observed in response to rapidly induced (< 30 s), brief (10 min), and moderate hypoxia (10% O2 in 90% N2) in 16 out of 42 study sessions in young (3- to 11-day-old) animals only. Responses to hypoxia were monitored over 4 consecutive days. In five cases, the latency to the onset of the ECoG depression increased progressively over the 4 test days, and its duration decreased progressively. An associated respiratory gasping pattern also exhibited gradual remission over consecutive days. These changes in the responses to repeated hypoxia demonstrate adaptation of mechanisms underlying neuronal perturbation by oxygen deprivation.

Adaptation, Physiological↗
PubMed1989

Disruption of the connections between the mediodorsal and sulcal prefrontal cortices alters the associability of rewarding medial cortical stimulation to place and taste stimuli in rats.

This study involved 2 tests of conditioned reward with self-stimulation (SS) of the prefrontal cortex. In Experiment 1, rats were tested for a conditioned taste preference (CTP) induced by pairing a novel flavor with SS of the medial prefrontal cortex (MC). Normal rats displayed a CTP. Rats with bilateral cuts of the connections between the MC and sulcal prefrontal cortex (SC) did not show a CTP. In Experiment 2, similar cuts had no effect on the ability of SC SS to promote a CTP, showing that the cuts spare the ability to learn a CTP. In Experiment 3, rats were tested for a conditioned place preference by pairing MC SS with environmental cues. Lesioned rats, but not intact rats, had a CPP. Results suggest the presence of prepotent relations, dependent on intrinsic prefrontal connections, between the rewarding effects of prefrontal stimulation and distinct sensorimotor domains.

Animals↗
PubMed1986

Distinct substrates influence the acquisition of self-stimulation of the hippocampus and the prefrontal cortex.

Self-stimulation (SS) of both the medial prefrontal cortex (MPFC) and the dorsolateral hippocampus (HPC) is known to develop slowly, over a period of days. In both cases, the acquisition of bar-pressing can be markedly hastened by delivery of noncontingent electrical stimulation for several days prior to SS training. The similarity of these effects suggests that there might be a common substrate mediating the acquisition process. However, in the present experiment, pre-training noncontingent electrical stimulation of the MPFC had no effect on how rapidly rats acquired the bar-pressing response for HPC stimulation, or vice versa. A further dissociation of the elements governing the acquisition process for these two SS sites was suggested by the observation that pre-training noncontingent stimulation of the entorhinal cortex facilitated the speed of acquisition of SS of the HPC but not of the MPFC. It seems that the HPC and entorhinal cortex can be excluded from the subset of neural structures which are known to influence the acquisition process governing MPFC SS. These and other data suggest that the development of SS of the MPFC and HPC can be regarded, at least in part, as involving a process rooted in distinct substrates.

Animals↗
PubMed1986

Behavioral measurement of axonal thresholds.

A behavioral method for measuring the electrical sensitivity of directly stimulated elements in the brain is described and applied to the medial forebrain bundle (MFB) reward path and the tectospinal circling path. Equations are derived from which threshold current densities may be calculated from knowledge of the electrode tip dimensions and the current required to produce criterion behavior, which is a function of electrode size. Four different sizes of electrode were implanted in the MFB of rats and self-stimulation rates plotted against stimulating current. The mean currents for criterion bar-pressing rates of 25% and 55% of maximum rate were determined for each electrode size and the values used to calculate average threshold current densities. Two sizes of electrode were implanted in the tectospinal tract of rats and the average currents to produce circling at 0.2 and 0.4 turns/s were measured. The threshold current densities for self-stimulation axons were about 5 times as large as those for circling, in accordance with other evidence that tectal circling path axons are larger than those of the MFB reward path.

Animals↗
PubMed1986

The role of corticocortical projections in self-stimulation of the prelimbic and sulcal prefrontal cortex in rats.

Four experiments were performed to assess the nature of the contribution of the corticocortical projections between the prelimbic and sulcal divisions of the rat prefrontal cortex to self-stimulation (SS) of these sites. The first experiment showed that transection of these projections by parasagittal knife cuts or bilateral electrolytic lesions of the prelimbic cortex had no effect on SS of the sulcal cortex. The second experiment demonstrated that SS of the prelimbic cortex could be obtained after transection of the corticocortical projection path. The third experiment demonstrated that the deficit in prelimbic SS, seen to follow such bilateral transections, is a function of the amount of exposure to the stimulation given to the animals after the lesion. The fourth experiment showed that the stimulation-dependent process underlying the acquisition of prelimbic and sulcal SS could be dissociated by the knife cuts. The discussion focused on the implications of these findings for an account of prefrontal self-stimulation behavior.

Animals↗
PubMed1986

Rat strain differences in the acquisition of hippocampal self-stimulation.

The rate of acquisition of lever-pressing for electrical stimulation of the hippocampus (HPC) was compared in two strains of rat: barrier-sustained Wistar and Sprague-Dawley. Sprague-Dawley rats initially bar-pressed at very low rates and took a median of 11 days to self-stimulate, according to the criterion used. Wistar rats all reached the same criterion in the first test session. Differential sensitivity to the activating effects of stimulation as an explanation for this difference was ruled out by the observation that both strains decreased response rates at the same rate and to the same level if stimulation was made non-contingent on lever-pressing. Differential threshold for reward was ruled out by the observation that rate-intensity curves yielded the same threshold currents and peak rates in both strains. Finally, it was shown that the rate of development of kindled seizures in the two strains of rats is different: Wistars kindle to full seizures faster than do Sprague-Dawleys. The relationship between the quicker onset of self-stimulation and of kindled seizures in Wistars is discussed.

Animals↗
PubMed1985

Effect of electrode size on brain stimulation.

Behaviorally determined strength-duration curves of many brain pathways differ from those of peripheral nerves, or single fibers. The chronaxies measured using short-duration pulses are much shorter than those measured with long pulses. A suggested explanation for this was that the pathways have mixed populations of long- and short-chronaxie elements. We attempted to test this hypothesis by stimulating with electrodes of different surface area, on the assumption that they would fire different proportions of long-chronaxie elements at short pulse durations where their thresholds are high. For a given current a large electrode delivers a lower maximum current density than a small one. Electrode size was found to have no detectable effect on the shape of the strength-duration curve. An attempt to discover the characteristics needed to modulate neurons having a basically hyperbolic strength-duration curve so as to produce the empirical curve revealed that the process has a zero rheobase and is thus presumably a direct influence of current on the threshold of the stimulated axons. A probable candidate for this process is the accumulation of potassium iontophoretically driven from cells in the vicinity of the electrode.

Animals↗