Stimulus-specific patterns of cardiovascular reactivity in type A and B subjects: evidence for enhanced vagal reactivity in type B.
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Biomedical subjects
Publications and source records attributed to J D Lane.
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To determine whether there are basic biological differences between Type A and Type B men, we compared hemodynamic, electrophysiologic and neuroendocrine responses to equipotent doses of isoproterenol (ISO) and norepinephrine (NE) in 10 Type A and 10 Type B men ages 18 to 29. Results showed equal hemodynamic and neuroendocrine responses to graded ISO doses in Type A and Type B individuals. In contrast, Type A men showed a more prolonged decrease in electrocardiographic T-wave amplitude (TWA) than did Type B men. Post hoc analyses of the correlates of TWA recovery during high-dose ISO infusion provide preliminary evidence for a more robust parasympathetic antagonism of sympathetic nervous system effects in Type B men, especially those with low scores on the Cook-Medley Ho scale. These findings suggest that, in addition to cognitively mediated increases in sympathetic nervous system reactivity, Type As may also be placed at increased risk of developing coronary heart disease by reduced levels of parasympathetic antagonism of sympathetic effects.
beta-Adrenergic hyperreactivity has been proposed as a pathogenic mechanism of increased coronary risk in Type A individuals. This study compared the effects of propranolol, diazepam, and placebo on cardiovascular and neuroendocrine responses to a stressful cognitive task in six young Type A males. Although diazepam did not differ from placebo, propranolol attenuated heart rate and norepinephrine responses and enhanced cortisol responses to the task. Findings suggest that propranolol has reciprocal effects on the norepinephrine and cortisol components of the "fight-flight" response. Possible central nervous system mechanisms are described.
Beta-adrenergic sympathetic nervous system (SNS) hyperresponsivity to behavioral stress may play a role in the onset of sustained high blood pressure--particularly in persons with a parental history of hypertension. Although hypertension is extremely prevalent among blacks, the association between parental history of hypertension and cardiovascular hyperresponsivity has not been explored in this group. The present study examined the influence of parental history of hypertension on cardiovascular stress reactivity in a group of young black females. Contrary to previous findings with whites, black subjects with a parental history of hypertension exhibited significantly smaller systolic blood pressure and forearm blood flow increases, and moderately smaller diastolic blood pressure increases to the task. Parental history subjects also exhibited slower heart rates throughout each experimental condition. The results suggest that blacks at risk from hypertension may not exhibit the beta-adrenergic hyperresponsivity to behavioral stress observed in whites. These results may suggest that beta-adrenergically mediated hyperresponsivity may be less involved in the development of hypertension among blacks.
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Adult male and female genetically seizure-prone rats were assessed for sound-induced seizures. Heterozygous control groups were compared with mild seizure (designated GEPR 3) and severe seizure animals (GEPR 9). Groups of animals were killed and crude synaptosome fractions (P2) prepared from freshly dissected cerebral cortices. Binding sites for gamma-aminobutyric acid (GABA) were assessed by [3H]-muscimol in the absence or presence of excess GABA and/or pentobarbital. Binding sites for benzodiazepines were assessed by [3H]-flunitrazepam in the presence or absence of clonazepam. Compared to controls, GEPR 3 animals had a modest increase and GEPR 9 animals a larger increase in Bmax for both high and low affinity GABA sites, with no change in Kd. Chloride-dependent, barbiturate-enhanced GABA binding (increased Bmax) was observed in all conditions and groups. Likewise benzodiazepine binding (Bmax) increased slightly in GEPR 9 animals. There were no observed changes in binding sites for a survey of biogenic amines. Seizure-prone animals appear to have compensatory denervation-like supersensitivity for their most prominent inhibitory receptor, which may or may not be linked to the seizure event.
The purpose of this study was to determine the effects of Type A behavior and family history of hypertension on cardiovascular reactivity to mental stress in a group of employed black women. Measures of heart rate and of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were taken at rest, during a mental arithmetic task, and during the Type A Structured Interview (SI). Results indicated that the Type A behavior pattern was associated with SBP and DBP hyperresponsivity during the SI but not during mental arithmetic. Additionally, certain speech components of the Type A pattern, as well as features of the potential-for-hostility component, were also related to cardiovascular responses during the SI. Family history of hypertension did not influence the cardiovascular parameters either alone or in combination with Type A behavior. The results suggest that many of the cardiovascular response characteristics of the Type A pattern that have been observed in predominantly white samples also hold true for blacks. Replication of these findings with other subgroups of blacks, such as young females and middle-aged males, will help document the generality of these findings within the black population.
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The function of dopaminergic innervations of the central medial nucleus accumbens in the processes maintaining intravenous morphine self-administration was assessed by lesioning with 6-OHDA and comparing drug intake with sham-vehicle treated littermates. Localized bilateral lesions of this structure resulted in significant increases in morphine intake shifting the dose-effect relationship to the right with twice the dose necessary to maintain prelesion rates of self-administration. Content of dopamine and dihydroxyphenylacetic acid was decreased in the nucleus accumbens after the lesion, but unchanged in the adjacent pyriform cortex and anterior caudate nucleus-putamen, while serotonin was significantly decreased in the pyriform cortex. High affinity uptake measurements also suggested nucleus accumbens dopaminergic and pyriform cortex serotonergic innervations to be affected by the lesion. The shift to the right in the dose effect relationship after the lesion suggests these neuronal systems to be excitatory to the processes mediating self-administration.
The Type A behavior pattern and the inhibited power motive have been implicated in the development of coronary heart disease (CHD). Since it is widely believed that enhanced cardiovascular responsivity may be one mechanism by which individuals develop CHD, the present study examined the relationship of Type A behavior and the inhibited power motive to different patterns of cardiovascular response during two behavioral tasks. Forty-one (24 Type A's, 17 Type B's) male undergraduates underwent the Type A structured interview (SI) and the Thematic Apperception Test (TAT) while a broad range of cardiovascular functions were simultaneously recorded. Different patterns of cardiovascular response were observed during the SI and TAT, and Type A's showed a greater tendency than Type B's to exhibit increased heart rate (HR), systolic blood pressure (SBP), and forearm blood flow (FBF) during the SI and the preparatory phase (but not the story-telling phase) of the TAT. The inhibited power motive was not related to enhanced cardiovascular responsivity during the SI or TAT. The implications of these findings for the development of CHD are discussed.
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Responding by six rats was maintained under a concurrent chained fixed-ratio 1, fixed-ratio 9 schedule (conc chain FR1 FR9 ) of food, water, and morphine presentations. The subjects had continuous access to the schedule contingencies on a reversed 12-h light-dark cycle. Local rates and temporal patterns were very similar for responding maintained by the three reinforcers with food and water intake occurring predominantly during the dark cycle, while morphine infusions were evenly distributed. Food and water extinction (24-h duration) decreased the number of ratios completed on both the food and water levers. Moreover, food extinction resulted in a large increase in I.V. morphine self-administration. Morphine extinction increased responding on the morphine lever while almost eliminating responding on the water lever. Changes in the dose of morphine (2.5-40 mg/kg/injection) did not significantly affect food and water intake, but were inversely related to responding on the morphine lever. Saline substitutions resulted in effects similar to those observed during morphine extinction. The schedule used in this study provides a method for examining the specificity of a number of pharmacological and neurochemical manipulations.
Acetylcholine (ACh) turnover rates were measured in fourteen brain regions of rats intravenously self-administering morphine and in yoked-morphine and yoked-vehicle infused littermates to identify cholinergic neuronal pathways potentially involved in opiate reinforcement processes. Rats receiving chronic passive administration of morphine had increased ACh turnover rates in the frontal cortex and diagonal band and decreased rates in the medial septum. The significant changes in animals self-administering the drug were prominent in limbic regions with increases in the frontal cortex and decreases in the pyriform cortex, nucleus accumbens, amygdala and ventral tegmental area. Some components of opiate reinforcement may be mediated by increases in the activity of cholinergic ventral pallidal and diagonal band fibers innervating the frontal cortex and by decreases in activity of cholinergic fibers innervating the ventral tegmental area. These data and turnover rates for dopamine, norepinephrine, serotonin, aspartate, glutamate and gamma-aminobutyric acid previously determined in similarly treated animals are consistent with two neuronal circuits that may be involved in opiate seeking behaviors and opiate reinforcement processes.
Muscarinic cholinergic and benzodiazepine receptor affinities and densities were evaluated in membranes from seven brain regions of rats intravenously self-administering morphine and in littermates receiving yoked-morphine or yoked vehicle infusions to identify neuronal systems potentially involved in mediating opiate reinforcement processes. Passive morphine infusion resulted in increases in muscarinic cholinergic receptor densities in the pyriform cortex and in decreases in the cingulate cortex while benzodiazepine receptor densities were decreased in both the hippocampal formation and entorhinal-subicular cortex compared to littermates receiving passive infusions of vehicle. Morphine self-administration resulted in decreased muscarinic cholinergic receptor densities in the frontal and entorhinal-subicular cortices and increases in the amygdaloid complex compared to littermates receiving yoked passive drug. These data are in agreement with acetylcholine turnover rate measurements in these animals and support the proposed role of cholinergic innervations of the frontal and entorhinal-subicular cortices and amygdaloid complex in opiate reinforcement processes.
Microinfusions of the endogenous opiate neurohumor, methionine enkephalin, into the nucleus accumbens initiated a reinforcing stimulus in a dose-related manner. The reinforcing nature of this intracranial self-administration was evaluated with intermittent schedules of reinforcement and a two-lever discrimination procedure. Opiate receptors are likely responsible for the initiation of this reinforcing stimulus since naloxone effectively blocked self-administration. These data suggest the mediation of opiate reinforcement through interactions with opiate receptors in brain regions outside the ventral tegmental area, questioning the current dopamine hypothesis for the initiation of these reinforcement processes.
Rats trained to discriminate pentylenetetrazol (PTZ) from saline in a two-lever food-reinforced operant task were given a three-day course of morphine, 15 to 45 mg/kg tid, ip. On the third day naloxone produced dose-dependent generalization to the PTZ stimulus, with 66% of subjects selecting the PTZ lever after the highest dose (0.32 mg/kg). Following termination of morphine injections, generalization of spontaneous withdrawal was tested. Approximately 50% of subjects selected the PTZ lever at 24 and 48 hrs after the last morphine, and by 96 hrs the percentage of subjects selecting the PTZ lever had dropped to 11%. Rats that chose the PTZ lever at 48 hrs were given diazepam, 5.0 mg/kg, which blocked the PTZ-like stimulus. These data demonstrate that morphine withdrawal produces a stimulus with PTZ-like characteristics which can be blocked by an anxiolytic, and they suggest that the PTZ discrimination may have general utility for investigating drug dependence and withdrawal in animals.
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