We tested the hypothesis, motivated in part by a coordinated computational cough network model, that alterations of mean systemic arterial blood pressure (BP) influence the excitability and motor pattern of cough. Model simulations predicted suppression of coughing by stimulation of arterial baroreceptors. In vivo experiments were conducted on anesthetized spontaneously breathing cats. Cough was elicited by mechanical stimulation of the intrathoracic airways. Electromyograms (EMG) of inspiratory parasternal, expiratory abdominal, laryngeal posterior cricoarytenoid (PCA), and thyroarytenoid muscles along with esophageal pressure (EP) and BP were recorded. Transiently elevated BP significantly reduced cough number, cough-related inspiratory, and expiratory amplitudes of EP, peak parasternal and abdominal EMG, and maximum of PCA EMG during the expulsive phase of cough, and prolonged the cough inspiratory and expiratory phases as well as cough cycle duration compared with control coughs. Latencies from the beginning of stimulation to the onset of cough-related diaphragm and abdominal activities were increased. Increases in BP also elicited bradycardia and isocapnic bradypnea. Reductions in BP increased cough number; elevated inspiratory EP amplitude and parasternal, abdominal, and inspiratory PCA EMG amplitudes; decreased total cough cycle duration; shortened the durations of the cough expiratory phase and cough-related abdominal discharge; and shortened cough latency compared with control coughs. Reduced BP also produced tachycardia, tachypnea, and hypocapnic hyperventilation. These effects of BP on coughing likely originate from interactions between barosensitive and respiratory brainstem neuronal networks, particularly by modulation of respiratory neurons within multiple respiration/cough-related brainstem areas by baroreceptor input.

Background: Nicotinic acetylcholine receptors are activated by agonists at an orthosteric site and modulated by ligands at allosteric sites. Results: We identify amino acids required for the coupling between orthosteric and allosteric sites. Conclusion: Allosteric activation can occur even when the orthosteric binding site is nonfunctional. Significance: Insights are provided into the cooperative functions of orthosteric and allosteric activators of the ␣7 nAChR.

There is evidence for a role of insulin and leptin in food intake, but the effects of these adiposity signals on the brain reward system are not well understood. Furthermore, the effects of insulin and leptin on food intake in females are underinvestigated. These studies investigated the role of insulin and leptin in the ventral tegmental area (VTA) and the arcuate hypothalamic nucleus (Arc) on food intake and brain reward function in female rats. The intracranial self-stimulation procedure was used to assess the effects of insulin and leptin on the reward system. Elevations in brain reward thresholds are indicative of a decrease in brain reward function. The bilateral administration of leptin into the VTA (15-500 ng/side) or Arc (15-150 ng/side) decreased food intake for 72 h. The infusion of leptin into the VTA or Arc resulted in weight loss during the first 48 (VTA) or 24 h (Arc) after the infusions. The administration of insulin (0.005-5 mU/side) into the VTA or Arc decreased food intake for 24 h but did not affect body weights. The bilateral administration of low, but not high, doses of leptin (15 ng/side) or insulin (0.005 mU/side) into the VTA elevated brain reward thresholds. Neither insulin nor leptin in the Arc affected brain reward thresholds. These studies suggest that a small increase in leptin or insulin levels in the VTA leads to a decrease in brain reward function. A relatively large increase in insulin or leptin levels in the VTA or Arc decreases food intake.

We investigated the influence of microinjection of codeine into the caudal ventral respiratory column (cVRC) on the cough reflex. Experiments were performed on 36 anesthetized spontaneously breathing cats. Electromyograms (EMGs) were recorded bilaterally from inspiratory parasternal and expiratory transversus abdominis (ABD) muscles and unilaterally from laryngeal posterior cricoarytenoid and thyroarytenoid muscles. Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airways. The unilateral microinjection of codeine (3.3 mM, 20-32 nl) in the cVRC reduced cough number by 29% (P < 0.01) and expiratory cough amplitudes of esophageal pressure by 33% (P < 0.05) as well as both ipsilateral and contralateral ABD EMGs by 35% and 48% (P < 0.01 and P < 0.01, respectively). No cough depression was observed after microinjections of vehicle. There was no significant effect of microinjection of codeine in the cVRC (3.3 mM, 30-40 nl) on ABD activity induced by a microinjection of D,L-homocysteic acid (30 mM, 27-40 nl) in the same location. However, a cumulative dose of codeine (0.1 mg/kg, 330 nmol/kg) applied into the brain stem circulation through the vertebral artery reduced the ABD motor response to cVRC D,L-homocysteic acid microinjection (30 mM, 28-32 nl) by 47% (P < 0.01). These results suggest that 1) codeine can act within the cVRC to suppress cough and 2) expiratory premotoneurons within the cVRC are relatively insensitive to this opioid.