The object of this experiment is to study the autonomic nervous control of alpha responses elicited in classical conditioning. Twenty-two mongrel dogs were trained in classical discriminative conditioning. Typical two-phase tachycardic responses were observed in positive (CS+) trials while only the earliest, phase 1, response was observed in negative (CS-) trials. The phase 1 response, which was identical in CS+ and CS-trials, was compared in dogs before and after selective SA-nodal parasympathectomy (N = 7) and beta-adrenergic blockade (N = 11). The phase 1 tachycardic response was eliminated by selective SA-nodal parasympathectomy but not by beta-adrenergic blockade. We conclude that the phase 1 response observed in both CS+ and CS-trials with similar time sequence and magnitude is an alpha response. The heart rate orienting response results from a withdrawal of parasympathetic activity with little or no change in sympathetic tone.

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Potentiation of the pressor response to stress by tolbutamide in dogs.

Tolbutamide has previously been shown to amplify the pressor effects of "exogenous" catecholamines in conscious dogs, possibly due to sensitization of the alpha 1-adrenoreceptor-mediated vasoconstriction. The objective of this study was to examine if tolbutamide also amplifies the pressor effects of "endogenous" catecholamines released during psychological stress (classical Pavlovian aversive conditioning). Experiments were conducted in beta-adrenoreceptor-blocked (propranolol, 1 mg/kg, i.v.) conscious dogs (n = 4) trained in classical aversive conditioning. Conditioning was accomplished by following a tone (CS+) with a 1/2 second shock; another tone (CS-) was not followed by any shock and served as control. With saline pretreatment, aversive conditioning (i.e., CS+) increased mean arterial pressure (MAP) only by approximately 4.7% when compared to CS-, whereas with tolbutamide (45 mg/kg, i.v.) pretreatment, the increase in MAP induced by CS+ beyond what was induced by the CS- (approximately 6.2%) was significantly (p < 0.05) larger than that with saline pretreatment. In isolated canine femoral arterial segments (n = 4), the vasoconstrictor effect of phenylephrine (an alpha 1-agonist) at 5 x 10(-6) M (which was the EC50 value) was amplified by 2 x 10(-2) M of tolbutamide from 54.0 +/- 2.0% to 66.9 +/- 2.1%. In conclusion, tolbutamide amplifies the pressor effects of "endogenous" catecholamines in conscious dogs, possibly by sensitization of the alpha 1-adrenoreceptor-mediated vasoconstriction. This mechanism of action is novel and has not been reported with other agents.

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Two-component arterial blood pressure conditional response in rat.

The objective of these experiments was to quantify the pattern of change in arterial blood pressure (BP) during a discriminative aversive classical conditioning paradigm in rat using a new "high resolution" computer analysis. Sprague-Dawley rats (n = 5) were restrained in a soft, conical cloth pouch and conditioned using a 6 sec. pulsed tone (CS+) followed by a 0.5 sec. tail shock; a steady tone, never followed by shock, served as a CS-. BP peaked at 16.4 +/- 6.5 mm Hg (mean +/- SD) above control at 1.5 +/- 0.1 sec. after onset of CS+. This "first component" ("C1") also occurred during CS- (12.1 +/- 3.8 mm Hg), although the magnitudes of the two were significantly (p < 0.05) different. Another group of rats (n = 8) was treated identically except the tones were 15 seconds long. The conditional BP response consisted of two components. C1 was reminiscent of that seen using the short tone: for CS+ a peak of 13.6 +/- 5.6 mm Hg at 1.5 sec. or, for CS-, of 10.0 +/- 4.3 at 1.3 sec. (p < 0.05). In CS+ trials BP peaked again ("C2," 7.4 +/- 2.5 mm Hg) at 8.3 +/- 1.2 sec. There was no statistically significant C2 for CS- trials, clearly demonstrating discrimination between tones. The unconditional BP response in both groups consisted of two large, closely spaced peaks in BP. Respiration was recorded in 3 additional rats. After shock delivery these subjects often showed a sudden shift between (1) a regular respiratory pattern with moderate chest excursion and (2) apneic episodes interspersed with single, deep breaths. This latter pattern was associated with large, low frequency fluctuations in BP. Continued development of the rat conditioning paradigm is especially warranted because of the ability to record sympathetic nerve activity in intact, awake subjects and the large number of readily available genetic strains, which model human pathological states.

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Cardiovascular dynamics during classical appetitive and aversive conditioning in laboratory primates.

This report describes changes in the rate of rise of left and right intraventricular pressures during aversive and appetitive conditioning procedures in chair-restrained rhesus monkeys. The conditioning paradigm consisted of a one-minute tone followed, in the one case, by an electric shock, and in the other, by the delivery of Purina monkey pellets. The conditional cardiovascular response was characterized by short latency, highly significant elevations in the derivatives of both ventricular pressures as well as a marked arterial pressor response and tachycardia. The magnitude of the conditional response to the classical aversive procedure was somewhat larger than that to appetitive conditioning. These alterations in the rate of development of intraventricular pressure can be attributed largely to augmentation in the sympathetic neural input to the heart and contribute to an analysis of selective aspects of the nervous regulation of the heart in intact, behaviorally conditioned animals.

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Acquisition and discrimination of appetitively and aversively conditioned heart rate responses in rhesus monkeys.

This report describes the acquisition of a conditional heart rate response to both classical aversive and appetitive conditioning in eight rhesus monkeys (Macaca mulatta). The behavioral paradigm consisted of two discrete one minute tones followed by the corresponding unconditional stimuli, i.e., electric shock or Purina monkey chow. A third tone followed by neither food nor shock served as a discriminative stimulus (DS). The conditional heart rate responses developed in two phases. The first phase was characterized by similar responses to both conditional stimuli and the DS. Control heart rate rose during this period. During the second phase, control heart rate decreased (five animals), the DS response disappeared, and different conditional heart rate patterns to food and shock emerged. The existence of distinct conditional response patterns indicates probable differences in the autonomic nervous regulation of the heart during aversive and appetitive conditioning.

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Cardiac arrhythmias in the monkey during classically conditioned fear and excitement.

Rhesus monkeys (Macaca mulatta) were tested in classic aversive and appetitive conditioning paradigms following complete coronary artery occlusion (CO) to test the hypothesis that "emotional stress" induces ventricular arrhythmias. Findings were based upon conditioning trials conducted for one or more weeks after occlusion in 13 animals. When all data from each animal for the week following CO were considered, there was no demonstrable tendency for arrhythmias to increase during "fear" conditioned to unavoidable electric shock or during "excitement" in anticipation of food. However, selected trials from six monkeys did reveal instances when changes in the frequency of occurrence of arrhythmias were coupled with behavioural conditioning. While analysis of these trials did not reveal any simple relationship between emotional stress and the development of ventricular arrhythmias after myocardial infarction, certain of the behavioral situations may be more potentially arrhythmogenic than others. For these selected trials, with respect to control, the number of arrhythmias may have increased or decreased upon presentation of the conditional stimulus; the exact response appears to depend upon the immediate physiologic status of the animal as well as on the behavioral condition. "More stressful" situations, such as aversive conditioning, are not necessarily associated with greater numbers of arrhythmias than were "less stressful" situations, such as appetitive conditioning. Arrhythmias appear to occur more frequently when an animal's heart rate is within a given range; this may reflect underlying cardiac sympathetic and parasympathetic nerve activity.

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Classic aversive conditioning of coronary blood flow in mongrel dogs.

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A note on ECG changes observed during Pavlovian conditioning in a rhesus monkey following coronary arterial occlusion.

Changes in the ECG of a rhesus monkey during a classical aversive conditioning trial conducted 10 minutes after occlusion of the marginal branch of the left circumflex coronary artery have been observed. This appears to reflect an instance where myocardial ischemia following coronary occlusion was exacerbated by presentation of a conditional stimulus.

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