COCAINE EFFECTS ON CNS-RELATED CARDIORESPIRATORY CONTROL

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The objective of these studies is to examine central neural control over respiratory and cardiac patterning following acute cocaine administration in freely moving cats. This objective is based on the assumption that cocaine alters activity in limbic system structures which normally have an influence on cardiac and respiratory patterning, and that death from cocaine administration may result from CNS effects on either the upper airway or diaphragmatic musculature, or from central effects on cardiac rhythms, perhaps compounded by peripheral vasoconstriction or hyperthermia induced by cocaine Dose-responses of cocaine will be assessed in relation to patterning of the upper airway musculature and the diaphragm, as well as to blood pressure, heart rate, and arrhythmias. EEG and single-neuron discharge will be examined in limbic and brainstem structures while have been demonstrated to have roles in cardiovascular and respiratory patterning. These structures include the central nucleus of the amygdala, the nucleus parabrachialis medialis of the pons, the nucleus of the solitary tract, and the hypoglossal nucleus. Electromyograhic activity of upper airway muscles including the posterior cricoarytenoid muscles, the major laryngeal dilator, and the thyroarytenoid muscle, a laryngeal constrictor, will be recorded, together with activity of the costal diaphragm. Arterial pressure will be recorded from an indwelling carotid cannula, and the ECG will be acquired from the diaphragmatic EMG leads. Core and anterior hypothalamic temperature will be monitored with miniaturized themprobes. Low, medium, and high doses of cocaine or control saline will be injected IV, and electrophysiological activity will be recorded for 24 hr post delivery. Pontine and amygdala sites will be reversibly blockaded by cooling following cocaine administration to examine the role of these structures in mediating cardiac and respiratory effects. Data will be written on a polygraph, digitized on a PDP 11/73 computer, and analyzed with respect to dose-related 1) inspiratory and expiratory timing alterations in the upper airway and diaphragm, 2) obstruction of the upper airway, 3) apneustic or apneic activity of the diaphragm, 4) alterations in phasic or tonic arterial pressure, 5) cardiac arrhythmias, 6) hyperpyrexia, 7) activated EMG or seizure discharge in limbic and brainstem areas, and 8) respiratory-related single neuron discharge in limbic and brainstem areas.