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Biomedical subjects

J S Turkkan

Publications and source records attributed to J S Turkkan.

At least 37 records · Page 2Linked to original sources

Conditioned opponent responses: effects of placebo challenge in alcoholic subjects.

The present study continues a series of studies examining a number of variables that contribute to the demonstration of conditioned responses to alcohol in alcoholics. We pursued here the hypothesis that subjects receiving placebo in an environment previously associated with alcohol ingestion would exhibit conditioned responses as compared with subjects who had only received placebo in the environment. Further, we predicted that these conditioned responses would be opposite in direction to responses obtained during active drink sessions. Twelve subjects received active alcohol during session Days 1 through 4 and a placebo challenge on Day 5; the second group received placebo throughout sessions 1 through 5. On Day 1, heart rate and skin conductance were elevated following active alcohol ingestion as compared with placebo. On Day 5 following the placebo challenge, these physiological responses were significantly lower in the alcohol group as compared with the placebo group; the reversal of effects on Day 5 is suggestive of conditioned compensatory responses. Also, following the placebo on Day 5, desire to drink scores of the alcohol group were greater than those of the placebo group. The present data suggest that subjects exhibit conditioned compensatory responses when the environment signals alcohol availability. Results are consistent with Siegel's model of conditioned compensatory responses to repeated drug administration, and may help to account for some aspects of tolerance development and conditioned withdrawal.

Adult↗

Behavioral performance effects of antihypertensive drugs: human and animal studies.

Antihypertensive drug treatments have been reported in clinical investigations to produce adverse effects to a degree that causes hypertensive patients to discontinue medication. Many of the debilitating effects reported by patients appear to be of central nervous system origin, such as sedation, fatigue, memory loss and sensorimotor disturbances. Human and animal laboratory studies in the past two decades have been characterizing the psychotropic effects of antihypertensive medications with use of a wide range of behavioral techniques. Antihypertensive drug classes covered in this review are beta-adrenergic blocking agents, alpha-adrenergic agonists, diuretics, angiotensin-converting enzyme inhibitors and calcium channel blockers. While findings in animal studies show generally greater behavioral impairments after administration of alpha-adrenergic agonists in comparison with other drug classes, the few laboratory studies conducted with hypertensive subjects present a confusing picture. A need for further laboratory research with hypertensive subjects and, study of antihypertensive drug combinations is discussed.

Animals↗

Psychophysiological effects of oral ethanol in alcoholics and social drinkers.

The acute and extended effects of ethanol ingestion were examined in five alcoholic subjects, and five "social" drinkers. Six physiological and four subjective report measures were taken before, during and up to 90 min after the ingestion of ethanol in three doses and placebo. Findings showed that alcohol exerted significant dose-related physiological effects in the initial minutes of ingestion, and in extended analyses of physiological and subjective measures in both groups of drinkers. Alcoholics and social drinkers generally did not differ in their physiological responses to alcohol doses and placebo, while some evidence for tolerance to reported euphoric effects of alcohol in the alcoholic subjects was found. The possibility is raised that early physiological responses observed during ethanol ingestion may arise not only from pharmacological effects of the drink, but may also be evidence for conditional predrink responses.

Adult↗

Production and reversal of DOCA-salt hypertension in baboons.

We describe for the first time a non-human primate model of mineralocorticoid-salt hypertension. Baboons instrumented for chronic, direct measurement of arterial pressure, underwent sodium chloride loading (8.6 or 17.1 mEq/kg/day) by different routes for several weeks and deoxycorticosterone acetate (DOCA) 5 mg/2 days i.m., in addition to sodium chloride, for periods lasting up to several months. Salt loading alone at 8.6 mEq/kg/day had no chronic effect on mean arterial pressure (MAP). Salt loading at both doses in combination with DOCA produced increases in MAP within a few days which became progressively larger over weeks to months. DOCA-salt hypertension was associated with hyporeninemia and mild hypokalemia, without consistent changes in heart rate or plasma catecholamines. A biofeedback procedure applied to three animals failed to reduce tonic blood pressure. In two of these animals, administration of clonidine or atenolol also had no antihypertensive effect, whereas a diuretic combination (hydrochlorothiazide and triamterene) rapidly abolished the hypertension. The absence of amelioration of the hypertension by a central sympatholytic agent or a beta-adrenoceptor blocker, coupled with the absence of increased plasma catecholamines, suggests that increased sympathetic activity may not contribute to the hypertension in contrast with findings in lower animals but consistent with clinical reports.

Animals↗

Novel long-term cardiovascular effects of industrial noise.

Baboon subjects were instrumented with indwelling arterial catheters for continuous measurement of blood pressure and heart rate before, during, and after exposure to industrial noise eight hours daily. Initial exposure to noise produced transient, acute elevations of systolic and diastolic blood pressures and heart rates at noise onset, which habituated over the course of noise exposure. Chronic exposure to noise lowered blood pressure and heart rate not only during noise, but particularly after daily noise offset. Blood pressures returned toward baseline after noise exposure was terminated. Plasma catecholamines were also decreased during noise exposure. A control animal which received only masking noise did not demonstrate decreases in cardiovascular parameters. The possibility of classically conditioned associations of noise onset with feeding was discussed.

Animals↗

Discriminative control of hyperdipsic drinking in the baboon.

A baboon subject was surgically prepared with an arterial catheter and subsequently trained to elevate diastolic blood pressure with an operant schedule of food procurement and shock avoidance with associated discriminative stimuli. Blood pressure elevations developed in accordance with the requirements of the conditioning procedure. In addition, large-scale increases in water intake occurred on days when the conditioning sessions were in effect. Both blood pressure and water intake elevations were maintained when the conditioning procedure was changed to eliminate food reinforcement. Electrical monitoring of water spout contacts revealed that drinking occurred exclusively during response-produced SDS associated with food delivery, and did not occur either during response-produced SDS associated with electric shock, or during intertrial intervals. Because acute elevations in blood pressure preceded licking bouts, the drinking was not producing the pressor episodes. Overall, the data illustrate that drinking can occur in a systematic manner under the control of exteroceptive discriminative stimuli during non-skeletal response contingencies.

Animals↗

Hyperdipsia in the baboon during operant conditioning of blood pressure elevation.

Water intake was monitored in intact baboons during acquisition stages of blood pressure conditioning (Experiment 1) and during 24-hr periods (Experiment 2). Water intake was elevated during noncontingent food pellet delivery, and more so during early acquisition stages of operantly conditioned blood pressure elevations. Changes in blood pressure, heart rate, and water intake were found to correspond closely during conditioning sessions. Several possible sources of control over drinking are discussed, such as the role of food-related discriminative stimuli, and hypothalamic integration of cardiovascular hemodynamics, water ingestion, and thermal regulation.

Animals↗

Plasma lactate levels during baseline and blood pressure conditioning in the baboon.

Lactic acid in arterial blood, systolic and diastolic blood pressures, and heart rates of baboons were examined for three naive subjects, and for five experimental subjects during baseline conditions and during training to elevate diastolic blood pressure through operant conditioning methodology. Lactic acid and cardiovascular levels were determined at rest (9 a.m.), and at 12:30 and 3:00 p.m. (during conditioning sessions, for trained subjects). At rest (baseline) lactic acid levels and cardiovascular measures were similar for conditioned and naive subjects. During conditioning sessions, blood pressures but not heart rates were significantly elevated. Plasma lactate increased from morning to afternoon in both naive and trained subjects, but at three hours of conditioning, trained subjects had significantly higher lactate levels than when at rest and when compared to naive subjects at the same time of day. This study provides normative data for plasma lactate in the laboratory baboon and also indicates metabolic changes (which may be related to increased muscular work) as part of concurrent changes in multiple systems (e.g., neural, hormonal) which accompany conditioned blood pressure elevations.

Animals↗

Performance characteristics of conditioned blood pressure elevations in the baboon.

Operant conditioning of diastolic blood pressure elevation was accomplished in six baboons (Papio sp.) by a procedure using food delivery when diastolic pressure was maintained above a prespecified level, and shock delivery when diastolic pressure remained below that level. Data from steady-state performance indicated a rise in diastolic pressure by a median 22 mm Hg when the daily session was begun. Elevated levels of diastolic blood pressure and low shock frequencies were maintained throughout the 12-hour session. The frequency and duration of shifts in diastolic pressure to below criterion level were found to be variable during the first 1-2 hours but were stable throughout the remainder of the session. Heart rate had a phasic temporal pattern over the 12-hour session, characterized for most subjects by a rate increase at session onset followed by a rate decrease. Analysis of individual performance records showed that the blood pressure increases could occur without concomitant elevations in heart rate.

Animals↗

Classically conditioned heart rate responses in Macaca mulatta after beta-adrenergic, vagal and ganglionic blockade.

Heart rates of 5 rhesus monkeys (Macaca mulatta) were monitored during classical conditioning trials consisting of a visual conditioned stimulus followed after 10 sec by an electric shock to the tail. Heart rates typically increased at the onset of the visual stimulus, and returned to baseline before shock delivery. Autonomic blocking agents were subsequently administered; their effects on resting heart rates, and on acceleratory and deceleratory phases of the biphasic conditioned heart rate responses were examined, both in the raw data, and with a statistical regression technique. Beta-adrenergic blockade by propranolol lowered resting heart rates and was found, after regression analysis, to reduce the heart rate increase phase, and to weakly enhance the subsequent heart rate decrease phase of the conditioned response. Vagal blockade by atropine sulfate elevated resting heart rate, and markedly reduced both acceleratory and deceleratory heart rate phases of the conditioned responses. Ganglionic blockade by chlorisondamine also elevated resting heart rates (less than atropine), and almost completely eliminated conditioned heart rate changes. Several sources of evidence suggest a predominant vagal tone over resting heart rates, as well as mostly vagal mediation (with some sympathetic contribution) of the biphasic conditioned rate response.

Animals↗

Blood pressure hyperreactivity in non-human primates during dietary sodium combined with behavioral stress.

The potential for behavioral stress alone or combined with dietary salt to augment pressor reactivity to the onset of daily experimental sessions was examined in normotensive, intact baboons over the course of four months. During twice daily experimental sessions, adult male baboons experienced food/shock conflict such that lever pulling not only served to earn food, but was also occasionally punished with cued mild electric shock. Blood pressure and heart rate were measured during a baseline period of fixed-ratio food reinforcement (3 weeks), during conflict stress (2 weeks), and after dietary salt was added to the daily conflict protocol (CONFLICT + SODIUM, 3 weeks). Reactivity, i.e., acute changes in blood pressure and heart rate to the daily experimental sessions, was not evident during food reinforcement sessions nor during the CONFLICT stress alone condition. The addition of a high salt diet virtually doubled blood pressure increases and heart rate decreases to the onset of experimental sessions. Average reactivities during CONFLICT + SODIUM periods were 11.2/7.9% delta for SBP/DBP (systolic/diastolic blood pressure, mmHg), and -5.65% delta for HR (heart rate, BPM). Neither atenolol nor hydrochlorothiazide diuretic significantly altered cardiovascular reactivity during CONFLICT + SODIUM in comparison to a preceding non-drug CONFLICT + SODIUM period. When atenolol and diuretic effects were directly compared, atenolol mildly augmented, while diuretic mildly decreased DBP but not SBP reactivity during CONFLICT + SODIUM. Reactivity was eliminated after salt loading and behavioral sessions were terminated. These findings provide evidence that enhanced salt ingestion may synergistically act with behavioral stress to produce pressor hyperresponsiveness to otherwise benign environmental events.

Animals↗

Chronic effects of high salt intake and conflict stress on blood pressure in primates. A progress report.

The effects of combined behavioral stress and high dietary salt on blood pressure were examined in baboons (N = 4) over the course of 1 year. Either high salt diet (240 mEq Na+/day) or conflict stress were administered for 8 to 16 weeks, followed by high salt intake and stress combined. Mean arterial pressure (MAP) increased by 8 mmHg during high dietary salt alone, by 4 mmHg during stress alone, and increased further to 14 mmHg above baseline during combined salt and stress. Control baboons (N = 2) had no change in MAP across 47 weeks. The data indicate additive effects of chronic high dietary salt intake and behavioral stress on blood pressure in non-human primates.

Animals↗

Behavioral performance effects of verapamil in normotensive and renovascular hypertensive baboons.

Behavioral performances of normotensive and hypertensive adult male baboons were tested before, during, and following chronic oral dosing with verapamil. Performances during a five-color simultaneous match-to-sample task were measured for two doses (2.0, and 3.2 mg/kg/day) and vehicle. Each dose was administered for 21 consecutive days preceded and followed by 14-day baseline and recovery periods, respectively. Choice reaction times increased by 9% during the lower dose of verapamil, compared to vehicle; choice reaction times were unchanged at the higher dose. At baseline and during vehicle administration, the yellow and white stimuli were the most difficult to discriminate correctly; discrimination of these colors was slightly impaired by the lower, but not the higher dose of verapamil. Verapamil's behavioral effects were not modulated by blood pressure changes since both baboon groups showed equivalent changes in behavioral performance, but only renovascular hypertensive baboons showed blood pressure decreases. Verapamil appears to be an effective hypotensive and does not produce profound psychomotor impairment at clinically used doses during the first weeks of treatment.

Animals↗