Biomedical subjects

P M McCabe

Publications and source records attributed to P M McCabe.

At least 37 records · Page 2Linked to original sources

PubMed1995

Destruction of neurons in the VPM thalamus prevents rabbit heart rate conditioning.

The present study examined the role of the ventral posterior medial nucleus of the thalamus (VPM) in classical heart rate (HR) conditioning using an acoustic conditioned stimulus (CS) and a corneal air puff unconditioned stimulus (US). Previous research suggests that VPM neurons are activated during the presentation of a corneal air puff US. Rabbits were given ibotenic acid lesions in the VPM and subjected to one Pavlovian HR conditioning session. The results of the present study demonstrate that destruction of cell bodies in the VPM reduces HR conditioning to the level of a pseudoconditioning control without affecting HR baseline, or orienting responses to the CS. Lesions of the VPM also significantly augment the tachycardiac unconditioned response, suggesting that VPM lesions alter the somatosensory processing of the US.

Animals↗

PubMed1994

Modulation of neuronal firing in the medullary solitary complex by electrical stimulation of the hypothalamic defense and vigilance areas in rabbits.

The present study sought to establish functional connections between two regions in the hypothalamus associated with the cardiorespiratory concomitants of affective behavior, and neurons in the dorsal medulla thought to be involved in the mediation of the baroreceptor reflex. Single cell recordings were made in the solitary complex of the medulla (nucleus of the tractus solitarius and dorsal vagus nucleus) of anesthetized rabbits. An attempt was made to modulate the activity of these neurons by electrically stimulating two hypothalamic sites: the hypothalamic defense area (HDA) and the hypothalamic vigilance area (HVA). Responses of solitary complex neurons to a bolus injection of phenylephrine and an injection of physiological saline in a blind sac preparation were assessed in order to test for baroreceptor input. Electrical stimulation of the HDA or the HVA was found to decrease the firing rate of most solitary complex neurons that responded to hypothalamic stimulation. The cells that did show an increase in firing rate were responding to HVA stimulation. Ninety-two percent of the neurons in the solitary complex that responded to HDA or HVA stimulation were also affected by baroreceptor activation. The connections between the HDA, HVA and the solitary complex may account, in part, for the distinctive patterns of cardiorespiratory responses observed when stimulating these two hypothalamic regions.

Affect↗

PubMed1994

Basal and reactive plasma catecholamine levels under stress and anesthesia in rabbits.

The present study was undertaken to determine if electrical stimulation of the hypothalamic defense area (HDA) and baroreflex activation elicited by head up body tilt produced changes in plasma catecholamine (CA) levels in anesthetized rabbits. We also compared the effects of two anesthetics, isoflurane and sodium pentobarbital, upon basal and reactive CA levels, and upon autonomic reactivity. HDA stimulation was found to produce significant increases in plasma norepinephrine (NE) levels but not epinephrine (E) levels. Passive tilt was found to produce statistically significant increases in NE levels for both anesthetics used and a significant increase in E levels for animals anesthetized with isoflurane. Basal and reactive measurements provided evidence that pentobarbital has a more suppressive effect upon the autonomic nervous system than isoflurane: (a) Basal NE levels were significantly lower in pentobarbital anesthetized animals than in isoflurane-anesthetized animals; and (b) Baroreceptor sensitivity to a passive tilt stressor was significantly higher for animals anesthetized with isoflurane than for animals anesthetized with pentobarbital.

Anesthesia, General↗

PubMed1994

Comparison of peripheral blood flow patterns associated with the defense reaction and the vigilance reaction in rabbits.

The present study compared the skeletal muscle and visceral blood flow patterns elicited by electrical stimulation of the hypothalamic defense area (HDA) and the hypothalamic vigilance area (HVA) of the rabbit. Electrical stimulation of the HDA evoked a pressor response, tachycardia, hyperventilation, an increase in blood flow to the skeletal muscles and decreased blood flow to visceral organs. Stimulation of the HVA yielded a pressor response, bradycardia, inspiratory apnea and decreased blood flow to both the skeletal muscles and the viscera. Intravenous injections of atropine methyl nitrate significantly reduced the HVA-elicited bradycardia and the HDA-elicited increase in blood flow to the skeletal muscles, thereby providing evidence that the bradycardia was mediated by vagal efferents and that the rabbit has an atropine-sensitive cholinergic vasodilation system. The decrease of blood flow to the visceral organs associated with the defense reaction and vigilance reaction was reversed by intravenous injections of the alpha-1 receptor blocker prazosin.

Animals↗

PubMed1994

Stimulus dimensions of the cold pressor test and the associated patterns of cardiovascular response.

Hemodynamics of the cold pressor response in relation to its pain and nonpain stimulus components were investigated in normotensive college men using the foot and forehead cold pressor tasks. Mechanisms of pain- and non-pain-related increases in blood pressure were analyzed as residual effects of concurrent changes in total peripheral resistance and cardiac output. The identified partial relationships suggested that the response pattern associated with pain included positive change both in cardiac output and in total peripheral resistance, whereas the nonpain-related response was limited to an increase in total peripheral resistance. Analyses of individual differences in cardiovascular responses to pain further indicated that pain-related increments in blood pressure were mediated by a steeper rise in total peripheral resistance, an increase in heart rate, and an apparent increase in preload. At baseline, high reactors to pain manifested relatively elevated total peripheral resistance, diminished cardiac output, and an indication of a reduced inotropic state, suggesting that altered basal homeostasis may discriminate normotensive individuals displaying heightened cardiovascular reactivity to aversive cold stimulation.

Adult↗

PubMed1994

Recovery of sensorimotor function after distal middle cerebral artery photothrombotic occlusion in rats.

BACKGROUND AND PURPOSE: The purpose of the present study was to delineate the behavioral correlates of focal thrombotic occlusion of the distal middle cerebral artery in rats and to compare the pattern of deficits and subsequent recovery to that following proximal middle cerebral artery occlusion. METHODS: Ten Sprague-Dawley rats underwent photothrombotic occlusion of the distal middle cerebral artery with tandem occlusion of the common carotid arteries (dMCAO group); 10 animals served as operated controls. Beginning on postischemia day 2, animals were given a battery of five tests that assessed sensorimotor integration, attentional mechanisms, and muscle strength; testing continued twice weekly until day 30. Nine days of cognitive testing on the learning set of the water maze task were then given. Infarct volume and hemispheric atrophy were determined for each dMCAO animal. RESULTS: After ischemia, the dMCAO group exhibited significant behavioral deficits in posture reflex, ability to place a forelimb to various stimuli, limb adduction during rearing, and neglect of contralateral space. These deficits showed variable recovery rates. No deficits were observed in muscle strength or cognitive performance. The deficits and patterns of recovery were related to infarct location and to degree of hemisphere atrophy. CONCLUSIONS: The present study suggests that a battery of tests is necessary to fully characterize the pattern of behavioral deficits after focal cerebral ischemia. Location of infarct damage and associated degree of hemispheric atrophy were important variables in determining behavioral outcome. The present results are compared with those of the more traditional model of electrocoagulation of the proximal middle cerebral artery.

Animals↗

PubMed1993

Electrolytic and ibotenic acid lesions of the medial subnucleus of the medial geniculate prevent the acquisition of classically conditioned heart rate to a single acoustic stimulus in rabbits.

The present study examined the role of the medial subnucleus of the medial geniculate (mMG) in classical heart rate (HR) conditioning to a single acoustic conditioned stimulus (CS) in rabbits. Previous electrophysiological and neuroanatomical studies have implicated the mMG as a potential site of plasticity in forming the HR conditioned response (CR) to acoustic stimuli. In addition, several studies have found that bilateral lesions of the rabbit mMG prevent differential conditioning to acoustic stimuli, however animals still exhibit a significant bradycardiac response to the tones. In order to determine if the residual bradycardia seen in differential conditioning studies was due to learned responses or non-associative effects, rabbits with either bilateral electrolytic or ibotenic acid lesions of mMG, and animals with lesions outside of mMG (lesion control), were subjected to one session of single tone Pavlovian conditioning. In this paradigm, an acoustic CS was paired with an aversive unconditioned stimulus (US) in the conditioning groups, and in a pseudoconditioning group the CS and US were unpaired. The results suggest that bilateral lesions of mMG prevent the acquisition of the HR CR relative to control lesioned animals. The results also suggest that cells intrinsic to mMG are involved in conditioned bradycardia to a single tone, as well as in the discrimination between two tones, as reported previously. The lesion effects upon CRs are discussed with respect to other areas in the acoustic thalamus.

Acoustic Stimulation↗

PubMed1993

Differential patterns of dynamic cardiovascular regulation as a function of task.

In cardiovascular reactivity studies, interpretations of the processes supporting the blood pressure response may become problematic when systolic blood pressure, diastolic blood pressure, and heart rate all increase in response to a behavioral challenge. Therefore, in addition to evaluating these cardiovascular responses, this study examined cardiac output, total peripheral resistance and systolic time intervals derived from impedance cardiogram, electrocardiogram and phonocardiogram recordings during a speech stressor, a mirror tracing task, and a foot cold pressor test. All of the behavioral stressors elicited increases in blood pressure and heart rate, with the largest changes occurring during the overt speech. Based on the examination of the response patterns of the underlying hemodynamic variables it would appear that, in both men and women, the blood pressure increase during the speech preparation period was supported by increased cardiac output; the speech itself resulted in a mixed pattern of increased cardiac output and total peripheral resistance; whereas, the mirror tracing and cold pressor tasks produced increased total peripheral resistance. Although men and women produced similar response patterns to the behavioral challenges, sex differences in the estimates of myocardial contractility were observed during rest. These results provide evidence that different behavioral stressors can produce a distinct yet integrated pattern of responses, whose differences may be revealed, when impedance cardiography is used, to derive sufficient response measures for assessing dynamic cardiovascular processes.

Adult↗

PubMed1993

A computerized grid walking system for evaluating the accuracy of locomotion in rats.

A microcomputer-based system employing photoelectric devices to record rat movements and footfalls in the grid walking test paradigm was developed and evaluated. Behavioral data obtained from the system were: distance traversed on the grid, time taken to traverse the distance, number of footfalls, times of footfalls, positions of footfalls, durations of footfalls, and whether the footfall was due to a hind or a fore limb. Validation of the system was performed by comparing the data obtained from the videotape analysis with that obtained from the computerized system. Correlation coefficients between the data obtained from the two methods were found to be 0.92 for one observer, 0.84 for a second observer, and 0.88 with the mean of the two observers. An experimental study in which a group of rats was administered dorsal hemisection lesions of the spinal cord was also conducted. Animals in the lesion group took the same amount of time to cross the runway as the control animals, but made more footfalls per crossing and had longer durations per footfall. The studies validate the capacity of the computerized system to efficiently detect fine locomotory deficits, suggesting that it is a viable tool for the evaluation of neurological dysfunctions in experimental rats.

Algorithms↗

PubMed1992

Ibotenic acid lesions in the amygdaloid central nucleus but not in the lateral subthalamic area prevent the acquisition of differential Pavlovian conditioning of bradycardia in rabbits.

The present study examined the effect of ibotenic acid lesions in the amygdaloid central nucleus (ACe) or in the lateral zona incerta of the subthalamus (LZI) on the acquisition of differential Pavlovian conditioning of bradycardia in rabbits. Previous work has shown that bilateral electrolytic lesions in either ACe or LZI abolished the retention of conditioned heart rate (HR) responses. In order to determine whether these findings were due to destruction of cells intrinsic to ACe or LZI, ibotenic acid lesions were placed bilaterally in either structure or in control sites. Following recovery, animals were subjected to differential Pavlovian conditioning in which one tone (CS+) was paired with periorbital shock and a second tone (CS-) was presented alone. It was found that destruction of cell bodies in ACe, but not LZI, prevented the acquisition of the differential bradycardiac conditioned response. In addition, ACe lesions did not interfere with baseline HR, the HR orienting response, the HR unconditioned response to shock, or the concomitantly conditioned corneoretinal potential. The results of this study suggest that destruction of cells intrinsic to ACe selectively prevents the acquisition of differentially conditioned HR, and perhaps other conditioned responses related to conditioned arousal, but does not affect unlearned HR responses or specific somatomotor conditioned responses.

Amygdala↗

PubMed1992

Protective effects of brain hypothermia on behavior and histopathology following global cerebral ischemia in rats.

The present experiments were designed to assess whether brain hypothermia can reduce the behavioral and histopathological deficits associated with global forebrain ischemia. Animals were subjected to 12.5 min of four vessel occlusion (4VO) with moderate hypotension, and brain temperature maintained at either 37 degrees C (4VO-37) or 30 degrees C (4VO-30). Behavioral tests designed to assess forelimb reflexes and sensorimotor function were given on post-operative weeks 2 and 4. Beginning in week 5, the rats were trained on a variety of navigation problems in the Morris water maze. Histopathological examination of the tissue 2 months following reperfusion revealed that 4VO-37 animals sustained substantial cell death in hippocampal region CA1 and moderate damage to the dorsolateral neostriatum. 4VO-30 animals showed minimal cell death in CA1 and neostriatum. There were no group differences for any of the sensorimotor measures, or for acquisition performance on either the simple place task or visible platform version of the water maze. In contrast, during acquisition of the learning set task, the performance of 4VO-37 animals was impaired relative to either of the other groups, whereas the performance of 4VO-30 animals was not significantly different from the sham controls. These data suggest that moderate intra-ischemic brain hypothermia provides long-lasting protection from behavioral deficits as well as neuronal injury following transient global ischemia.

Animals↗

PubMed1992

Sensorimotor and cognitive consequences of middle cerebral artery occlusion in rats.

Rats were subjected to either right proximal middle cerebral artery (MCA) occlusion or sham operation, and examined for an extended period on a battery of tests designed to measure simple motor function, sensorimotor integration and cognitive function. Rats with MCA occlusion showed extensive neuronal loss in the dorsolateral striatum and variable neuron loss in the parietal, temporal and frontolateral neocortex. MCA occluded animals exhibited significant impairments in tests of postural reflex, visual and tactile forelimb placing, locomotor coordination, and a test of simultaneous bilateral tactile extinction. The reflex and sensorimotor function deficits recovered to pre-operative levels by Day 30 post-ischemia. Five weeks following surgery, rats were tested in 2 versions of the Morris water task. Rats with MCA occlusion demonstrated significant impairments in their ability to navigate to a hidden platform, but were not significantly impaired on the visible (cued) version of the task. This general pattern of transient sensorimotor and reflex deficits, but with more persistent cognitive impairments, is similar to that seen in humans following MCA infarcts.

Animals↗

PubMed1992

Air puff versus shock unconditioned stimuli in rabbit heart rate conditioning.

The present study examined whether corneal air puff can be used as an unconditioned stimulus to elicit reliable classically conditioned heart rate (HR) responses in rabbits. The conditioned and unconditioned HR responses were assessed during Pavlovian conditioning with different intensities of paraorbital shock (2.7, 1.2, or 0.5 mA) or corneal air puff (18.3, 5.9, or 2.2 N/cm2) unconditioned stimuli (UCSs). Each experimental group was given one acquisition session during which an acoustic conditioned stimulus was paired with either the high, medium, or low intensity of a shock or air puff UCS. The results suggest that: a) HR is reliably conditioned with a high-intensity air puff UCS, and with medium- or high-intensity paraorbital shock stimuli; and b) only UCSs that elicit a tachycardiac unconditioned HR response reliably support HR conditioning. It was concluded that either air puff or paraorbital shock can serve as an effective UCS for HR conditioned responses.

Animals↗

PubMed1991

Electrophysiological evidence for hypothalamic defense area input to cells in the lateral tegmental field of the medulla of rabbits.

Single cell recordings were made from neurons in the lateral tegmental field of the medulla (LTFM) during electrical stimulation of the hypothalamic defense area (HDA) of the rabbit. Fifty-four cells were inhibited by HDA stimulation; 23 of these cells received barosensory input. Twenty-two LTFM cells showed an increase in firing rate during HDA stimulation; 10 of these cells received barosensory input. The results of this study provide evidence that the hypothalamic defense area makes functional connections with cardiovascular-influenced neurons in the LTFM.

Afferent Pathways↗

PubMed1991

Hypothalamic, midbrain and bulbar areas involved in the defense reaction in rabbits.

The present study mapped neuroanatomical sites in the hypothalamus and periaqueductal gray (PAG) of the rabbit which, when stimulated electrically, evoked the cardiorespiratory components of the defense reaction (CRDR). This included increases in heart rate, blood pressure, hindlimb blood flow and respiration rate. All of the components of the CRDR were elicited by electrical stimulation of the posterior hypothalamus, at sites dorsal and medial to the fornix. Although there were regions throughout the PAG in which electrical stimulation elicited concomitant increases in blood pressure, hindlimb blood flow and respiration rate, only stimulation of the dorsal PAG evoked tachycardia. Injection of horseradish peroxidase into the rostral ventrolateral medulla (RVLM) led to heavy retrograde and anterograde labeling in the region of the hypothalamus that yielded the CRDR when stimulated electrically. Heavy labeling was also observed in the dorsal and ventral PAG. The results of this study provide evidence that the posterior hypothalamus and the dorsal PAG are nodal structures in the mediation of the CRDR and that cells in posterior hypothalamus, dorsal PAG and ventral PAG make monosynaptic connections with the RVLM.

Agonistic Behavior↗

PubMed1991

Blood pressure reactivity and perception of pain during the forehead cold pressor test.

The relationship between blood pressure reactivity and the perception of pain was examined during a series of three forehead cold pressor tests given every other day to a group of 18 male college students. Subjects classified as high reactors on the basis of peak increases in mean blood pressure during cold pressor tests perceived the cold pressor stimulus as more painful than subjects classified as low reactors. The propensity to rate the cold pressor stimulus as painful was positively correlated with the individual level of blood pressure reactivity (baseline-free partial r = .62). Intra-individual correlations between pain and blood pressure responses were unrelated to subjects' reactivity status. Across the 3-min test, correlations between pain and blood pressure reactivity (with the effects of baseline blood pressure levels partialled out) were significant only during periods when levels of responses were relatively high. The heart rate responses were unrelated to pain ratings. Generalizability theory was applied to the analysis of temporal stability of cold pressor reactions. Both blood pressure and pain responses were highly reproducible across three sessions, appearing to express stable individual differences. The efficacy of 800 mg oral ibuprofen in controlling the cold pressor pain was also tested. Analgesic activity of the drug during the cold pressor test could not be demonstrated.

Adolescent↗

PubMed1991

Amphetamine promotes recovery from sensory-motor integration deficit after thrombotic infarction of the primary somatosensory rat cortex.

The present studies were undertaken to examine 1) whether d-amphetamine sulfate administered to rats well after thrombotic infarction of the vibrissal cortical barrel-field within the primary somatosensory cortex affected the rate and completeness of behavioral recovery and 2) whether a dose-response relation exists between d-amphetamine sulfate dose and recovery of function. In a learning task requiring sensory-motor integration, 41 rats were trained to perform a motor response in a T-maze consequent to the detection of a vibrissal deflection cue. Once training was complete, unilateral (n = 29) or sham (n = 12) infarction was produced by a noninvasive photochemical technique. After infarction, T-maze performance was assessed repeatedly in rats receiving 2 (n = 10) or 4 (n = 10) mg/kg d-amphetamine sulfate or saline (n = 9) 24 hours prior to testing on days 4, 6, 9, and 11. The sham-operated control rats received d-amphetamine sulfate (n = 7) or no injections (n = 5). All three infarcted groups displayed a reliable and sustained behavioral deficit in performance that was not present in the sham-operated control animals. Although the performance of each infarcted group improved over the testing sessions after the first injection, the amphetamine-treated groups improved at a faster rate than the saline-injected group. The results further demonstrated a dose-response effect, with the 4 mg/kg amphetamine group recovering to within preinfarction levels 6-8 days earlier than the 2 mg/kg amphetamine and saline-injected groups. Moreover, both amphetamine-treated groups recovered more completely than the saline-injected group. Quantification of the chronic infarct area revealed no differences among the amphetamine-treated and saline-injected groups. These data provide further evidence of the facilitatory effect of d-amphetamine sulfate on recovery from brain injury and extend this effect to the enhancement of recovery subsequent to thrombotic infarction of the primary somatosensory cortex.

Amphetamine↗

PubMed1990

Sensory-motor deficit and recovery from thrombotic infarction of the vibrissal barrel-field cortex.

The present studies were undertaken to examine: (1) whether thrombotic infarction of the vibrissal cortical barrel-fields of the primary somatosensory cortex would produce behavioral consequences reflecting a sensory-motor deficit; and (2) whether there was any recovery of function up to two months after infarction. Specifically, in two different learning tasks requiring sensory-motor integration, rats were trained to perform a motor response consequent to the detection of vibrissal cues derived from either active exploration or from passive detection of vibrissal deflection. Once training was complete, unilateral, bilateral or sham-infarction restricted to the region of the primary somatosensory cortex was produced by a non-invasive photochemical technique, which induces platelet-activated vascular occlusion combined with blood-brain barrier changes and subsequent cell death. The results demonstrated that, regardless of the active or passive sensory characteristics of the task, unilateral and bilateral infarction resulted in a reliable performance deficit, which was not present in sham-operated control animals. Thus, the infarct disrupted the ability to integrate passively received or actively acquired vibrissal sensory information with a previously associated motor response. However, unlike the bilaterally infarcted animals, who displayed no recovery of performance level throughout the postinfarction testing sessions, the unilaterally infarcted animals exhibited a gradual improvement in performance beginning in the second or third week postinfarction and recovering to within 10-20% of preinfarction levels between postinfarction days 46-61. The similarity of the temporal pattern of behavioral recovery in the unilateral groups, despite large differences in the sensory-motor demands of the two tasks, may reflect several common underlying mechanisms of recovery. Since similar sensory-motor behavioral deficits and recovery have been described with human stroke, the present model incorporates many of the pathophysiological and behavioral properties present in the clinical situation and may be useful for future investigation of therapeutic intervention.

Animals↗