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Biomedical subjects

R D Fitzgerald

Publications and source records attributed to R D Fitzgerald.

At least 19 recordsLinked to original sources

Learning versus performance effects of cocaine on discriminative heart rate conditioning in rats.

The study examined the effects of cocaine on learning and performance of a classically conditioned heart rate (HR) discrimination in rats involving two auditory conditioned stimuli (CSs). In the discrimination protocol, one CS (CS+) was paired with the shock unconditioned stimulus (US) on a consistent basis and the other CS (CS-) was always presented alone. Four groups received an IP injection of 1, 3, 10, or 30 mg/kg cocaine and a fifth group received saline. Shortly after the injections, all groups were given six CS-alone trials, followed by 24 randomly sequenced discrimination conditioning trials (12 CS+ and 12 CS-). Approximately 72 h later, all groups were given six test trials with each CS in the absence of cocaine to evaluate the presence or absence of discrimination learning. All cocaine groups showed impaired discrimination performance on the discrimination conditioning trials, reductions in early pretest CS-alone responses, and reductions in resting HR. However, on the non-drug test trials discrimination performance was normal in all cocaine groups. The results established that in spite of major changes in HR dynamics, learning of the HR discrimination was not affected by cocaine but that cocaine did interfere with the performance of the discrimination. Except for the highest 30 mg group, the performance decrement appeared to be related to a cocaine-produced reduction in the capacity to inhibit bradycardia responding to the safe CS-. It was suggested that this loss of inhibitory control may have been due to cocaine changes in a corticothalamic pathway that controls inhibition of bradycardia to a safe CS-.

Animals

Stress response to tracheal intubation: direct laryngoscopy compared with blind oral intubation.

Haemodynamic and hormonal responses to tracheal intubation can be profound and associated with serious cardiovascular and cerebral side effects. The Augustine Guide, a device enabling blind oral intubation, has been introduced recently. The aim of our study was to compare the haemodynamic and hormonal stress response of this method with direct laryngoscopy. Thirty five patients (ASA 1 and 2) were randomly assigned to undergo either direct laryngoscopy (n = 17), or blind oral intubation (n = 18). Haemodynamic responses and concentrations of adrenaline, noradrenaline and prolactin were determined prior to induction, before intubation and 5 min after intubation. The median duration of intubation was 22s for direct laryngoscopy vs 46s for blind oral intubation (p < 0.05). Between the groups, no significant differences were observed for heart rate, systolic or mean arterial blood pressure. Serum levels of adrenaline decreased slightly after induction and remained unaltered after intubation in both groups. Noradrenaline (1.01 vs 0.66 nmol.l-1) and prolactin (5.2 vs 2.9 nmol.l-1) levels were significantly higher after direct laryngoscopy compared to blind oral intubation. Although blind oral intubation took significantly longer to perform than direct laryngoscopy, hormonal stress response was less pronounced. Blind oral intubation should therefore not be withheld from patients with impaired cardiovascular reserve.

Adolescent

Cardiovascular and catecholamine response to surgery in brain-dead organ donors.

Eleven brain-dead organ donors were studied during surgery. Plasma levels of adrenaline and noradrenaline were measured before and after skin incision, upon sternotomy and 15, 30 and 45 min thereafter. Haemodynamic changes were measured continuously throughout the observation period. Blood pressure and heart rate increased after skin incision, remained high at sternotomy then decreased towards the end of the observation period in six of the 11 patients. Plasma catecholamines increased promptly with the onset of surgical stimuli. We conclude that surgical stress can evoke an excessive rise of plasma adrenaline and noradrenaline and thus could impair allograft function.

Adult

Excursions of the cervical spine during tracheal intubation: blind oral intubation compared with direct laryngoscopy.

The most appropriate technique for performing tracheal intubation in patients with cervical spine injury is debatable. Recently, a new device enabling blind oral intubation (Augustine Guide) with the patient's head and neck in the neutral position has been introduced. The aim of this study was to compare the extent of upper cervical spine movement during intubation with this device compared to direct laryngoscopy. Twelve patients (Mallampati I and II), without a cervical spine injury, were intubated using the Augustine Guide and afterwards by direct laryngoscopy. Both procedures were viewed radiographically. Extension in the upper cervical spine was determined at the point of the maximum excursion. By evaluating the joints occiput-C3 together as a functional unit, blind oral intubation caused 17 degrees (median) less extension compared to direct laryngoscopy (p < 0.01). The median differences observed for the individual joints were: 7 degrees in occiput-C1 (p < 0.05), 5 degrees in C1-2 (p < 0.01) and 6 degrees in C2-3 (p < 0.01) respectively. Since we assume that intubation-induced excursions of the injured spine are even higher, blind oral intubation might be a safe alternative for airway management in this special group of trauma victims.

Adult

Effects of centrally administered anxiolytic agents on classically conditioned bradycardia.

Rats received infusions of the opioid peptide D-Ala2-Met-enkephalinamide (DALA, 10 micrograms), the alpha 2-noradrenergic agonist clonidine (CLON, 3 micrograms), UK14,304 (UK, 5 micrograms), the corticotropin-releasing factor (CRF) antagonist alpha-helical CRF (9-41) (alpha-HEL, 25 micrograms), or saline in the rostral fourth ventricle. The DALA, CLON, and UK groups showed no evidence of a heart rate (HR) conditioned response (CR) during conditioning, after antagonist administration, or on a nondrug test 48 hr after conditioning. These three groups showed the development of normal CRs when later retrained without drugs. The alpha-HEL group showed an enhanced CR. During a subsequent startle test, the presence of a conditioned stimulus resulted in a pronounced suppression of startle in the SAL and alpha-HEL groups but had no effects on startle in the DALA, CLON, and UK groups. The results indicate an important role for fourth ventricle structures containing opioid and alpha 2 receptors in the learning of an HR CR.

Animals

Locus coeruleus involvement in the learning of classically conditioned bradycardia.

Opioid agonists are known to inhibit the activity of locus coeruleus (LC) neurons. In this study, microinjections of the mu-opioid agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO; 1.6 microM) bilaterally into the LC caused a significant impairment in the development of a heart-rate (HR) conditioned response (CR). The adverse effect of DAMGO on the HR CR could be reversed with naltrexone pretreatment. Microinjections of DAMGO into the periaqueductal gray, parabrachial nucleus, or fourth ventricle structures 1-2 mm away from the LC had no effects on the development of an HR CR. We conclude that central noradrenergic activity as mediated by the LC is critically involved in the learning and retention of conditioned cardiovascular responses.

Analysis of Variance

Impaired learning of classically conditioned bradycardia in rats following fourth ventricle administration of D-Ala2-methionine-enkephalinamide.

Prior to differential classical conditioning on two successive days, three groups of rats received an infusion (10 micrograms) of either the opioid peptide D-alanine2-methionine-enkephalinamide (DALA), DALA plus naltrexone (5 micrograms), or saline into the rostral region of the fourth ventricle. A fourth group, which served as a control to help localize DALA's site of action, received an infusion of DALA (10 micrograms) into the brain stem area on the floor of the ventricle. The group given DALA alone in the ventricle showed no evidence of a heart rate conditioned response (CR) either during conditioning or during a nondrug test session given 2 days after conditioning. Interference with the CR by DALA was reversed by the concomitant infusion of naltrexone. The control group given DALA in the brain stem developed a normal CR. It was suggested that DALA-induced opioid-receptor activity in the region of the periaqueductal/periventricular gray or locus coeruleus region of the ventricle may have prevented the learning of a CR. This could have occurred through a blunting of the emotional aftereffects of the unconditioned stimulus or through interference with projection pathways to other areas.

Animals

Morphine influences on classical aversive conditioned heart rate in rats.

The present series of three experiments was concerned with the effects of morphine and the morphine antagonist naloxone on the development of a classical aversive heart rate (HR) conditioned response (CR) to a tone conditioned stimulus (CS) paired with an electric shock unconditioned stimulus (US). In the first study, separate groups of rats received preconditioning sc injections of either 0.25 mg/kg, 5 mg/kg, or 10 mg/kg of morphine. Three other groups were given 0.1 mg/kg, 5 mg/kg, or 10 mg/kg of naloxone alone. All of the morphine groups showed attenuation HR responses to the CS on preconditioning CS-alone trials. During conditioning, the 10-mg/kg morphine group showed a markedly decremented bradycardia CR and tachycardia unconditioned response (UR), whereas the 5-mg/kg morphine group showed a normal CR in combination with a decremented UR. Naloxone had no measurable effects on HR. In the second study, naloxone (1 mg/kg) given after conditioning failed to reverse the CR and UR losses produced by 10 mg/kg of morphine given prior to conditioning. Administration of 10 mg/kg of morphine produced only a minor reduction in a HR CR established in a drug-free state, but the tachycardia UR was severely reduced. The results of the third study showed that 1 mg/kg of naloxone was effective in reversing analgesia induced by 10 mg/kg of morphine, as indexed by the tail-flick test. Taken together, the results suggest that the 10-mg/kg dose of morphine interfered with the learning of a HR CR, perhaps principally by reducing the aversive or emotional consequences of the shock US. Direct cardiovascular effects of morphine seemed to interfere with the performance of the tachycardia UR, but not with the performance of the bradycardia CR.

Acoustic Stimulation

Opposing heart rate reactions associated with behavioral states of excitation and inhibition.

Following the development of an excitatory bradycardia conditioned response (CR) to a CS+ paired with a shock US on Day 1, three groups of rats were given one of three inhibitory training procedures on Day 2 with a different CS (CS-). Then on Day 3 the inhibitory capacity of each CS- was examined on a modified combined cue test in which CS- was given slightly before CS+ and on a reversal conditioning test in which CS- was now paired with the US. The three inhibitory procedures consisted of CS- alone (CSA) trials, explicitly unpaired (EUP) CS- and US trials, and truly random (TR) CS- and US trials. During inhibitory training, the bradycardia CR to CS+ was replaced with a tachycardia reaction to CS- in the EUP group but not in the other groups. Subsequent to inhibitory training the EUP group and to some extent also the TR group showed a decrement in the excitatory bradycardia response to CS+ when compared to the robust HR slowdowns displayed by the CSA group. It was suggested, within the context of opponent process theory, that the separate USs given the EUP and TR groups (especially the former) during inhibitory training may have led to conditioning of inhibitory tendencies to CS- and that these in turn generalized and decremented previous established bradycardia responding to CS+ and the development of a new bradycardia to CS- during reversal conditioning.

Animals

Baroreceptor involvement in classically conditioned heart rate responses of restrained rats.

A group (N = 8) of restrained, baroreceptor denervated rats and a sham-operated-control group (n = 8) received discriminated classical conditioning consisting of 30 reinforced trials in which a CS+ was paired with an electric shock US and 30 non-reinforced trials in which a different CS (CS-) was presented alone. The control group displayed a decelerative heart rate CR and a biphasic pressor-depressor blood pressure CR. The denervated group failed to show a heart rate CR but did show a pressor-only blood pressure CR. The URs of the denervated group consisted of a major depressor change in blood pressure and a slight tachycardia whereas the URs of the control group consisted of a slight pressor response and tachycardia. The results indicated that centrally initiated activity in the efferent vagal pathways mediating the decelerative HR CR in rats may be blocked by the absence of normal afferent baroreceptor neural discharge. An integrating role of baroreceptor input was also suggested for the URs.

Animals

Effects of drug-induced changes in resting blood pressure on classically conditioned heart rate and blood pressure in restrained rats.

Subsequent to receiving aversive classical conditioning, which led to a decelerative heart rate (HR) conditioned response (CR) and a pressor-depressor blood pressure (BP) CR, three separate groups of restrained rats received intravenous infusion of sodium nitroprusside (40 micrograms/mg/min) to lower baseline BP, phenylephrine (17 micrograms/mg/min) to raise baseline BP, or an equivalent volume of saline. Conditioning test trials during infusion revealed that hypotension produced by sodium nitroprusside eliminated the HR CR and transformed the BP CR into a pressor-only reaction. Hypertension produced by phenylephrine facilitated the HR CR and changed the BP CR to a pressor-only response on selected trials in which baseline BP increases and baseline HR decreases were within restricted limits. Following drug withdrawal, the HR CRs of both drug groups and the BP CR of the phenylephrine group were attenuated. The unconditioned responses to the shock unconditioned stimulus under phenylephrine were exaggerated and consisted of tachycardias and depressor BP changes, whereas under sodium nitroprusside reduced tachycardias and depressor activity occurred. The results suggested that the loss of the vagally mediated HR CR under sodium nitroprusside was due to baroreceptor-controlled inhibition of vagal discharge and that the enhancement of the HR CR under phenylephrine was due to baroreceptor-influenced facilitation of vagal discharge.

Animals

Pavlovian conditioning with ethanol and lithium: effects on heart rate and taste aversion in rats.

Rats received paired injections of either ethanol or saline as the conditioned stimulus and lithium chloride as the unconditioned stimulus (US) in a Pavlovian differential conditioning paradigm. Lithium chloride evoked a large deceleration in heart rate (80-100 beats per minute) as an unconditioned response. As a result of 10 conditioning trials, the substance paired with LiCl elicited a lower average heart rate than that elicited by the unpaired substance. Moreover, animals that received ethanol-LiCl injections subsequently were more averse to the taste of ethanol than animals receiving saline-LiCl pairings. However, there were no differences in ethanol's ability to serve as the US to induce an aversion to a novel flavor solution (i.e., the Avfail phenomenon was not observed). The overall pattern of results underscores the value of using multiple indexes of learning in drug-drug conditioning paradigms.

Animals

Effects of restriction of maternal uterine blood supply on postnatal conditioning of heart rate and behavioral development in dogs.

An examination was made of the heart rate responses during aversive classical conditioning of 5- to 6-week-old Labrador puppies exposed to restricted maternal uterine blood supply during gestation. The direction of the heart rate responses of the treated puppies was consistently decelerative, whereas nontreated controls showed both decelerations and accelerations. The absence of accelerative heart rate changes, combined with the observed depression of base level heart rate and attenuated emotional behavior in the experimental animals relative to controls suggests that uterine blood supply insufficiency may have impaired normal autonomic development in utero.

Animals

Autonomic control of heart rate and blood pressure in spontaneously hypertensive rats during aversive classical conditioning.

An examination was made of the heart rate (HR) and blood pressure (BP) responses of 7-9-wk-old spontaneously hypertensive rats (SHR) and genetical control Wistar/Kyoto (WKY) rats during aversive classical conditioning. Subsequent to the development of conditioned responding (CRs), assessments were made of the effects of selective autonomic blockade by methyl atropine (10 mg/kg), phentolamine (2 mg/kg), and propranolol (2 mg/kg). The CR complex in the two strains consisted of pressor BP CRs in conjunction with vagally mediated decelerative HR CRs in the SHR strain and sympathetically mediated accelerative HR CRs in the WKY strain. The decelerative SHR HR CR did not appear to be secondary to baroreceptor reflex activity, although such activity did appear to be involved in the pressor BP and decelerative HR orienting response (OR) and unconditioned response (UR) complex of the SHRs on the initial application of the CS and the US, respectively. Augmented pressor BP ORs, CRs, and URs in the SHRs relative to the WKYs and differential drug effects on BP and HR baselines of the two strains suggested the presence of enhanced sympathetic activity in the SHRs that was not reflected in the SHR decelerative HR CR. Phentolamine unmasked evidence of reflex beta 2-vasodilation deficiency in the SHRs that could have contributed to the enhancement of their BP OR and CR.

Animals

Group process in teaching family dynamics to family practice residents.

Behavioral science training in family practice at Madigan Army Medical Center, Tacoma, Washington, has used small group seminars to teach family dynamics on an experiential level. The group process is similar enough to dynamics within families to facilitate understanding by introspection. Small groups are an efficient method for teaching, and allow experiential learning to occur spontaneously as well as on a planned basis.

Family