D1/D2-dopamine receptor agonist dihydrexidine stimulates inspiratory motor output and depresses medullary expiratory neurons

Abstract

It is now accepted that dopamine plays an important neuromodulatory role in the central nervous control of respiration. D1, D2, and D4 subtypes of the receptor seem to be important players, but the assignment of various respiratory tasks to specific subtypes of the dopamine receptor is a work in progress. In the present investigation, dihydrexidine (DHD), a full dopamine receptor agonist with affinity for both D1- and D2-subtypes of receptor, was tested for its effects on inspiratory neurons and motor output and on membrane potential properties of medullary bulbospinal expiratory augmenting expiratory neurons in the pentobarbital anesthetized adult cat. The effects of DHD were compared with those of the highly selective D1-dopamine receptor (D1R) agonists SKF-38393 and 6-chloro-APB. DHD increased the intensity and duration of inspiratory motor output. Phrenic nerve discharge intensity was increased and prolonged, contributing to elevated inspiratory effort and duration when spontaneous breathing was monitored with tracheal pressure measurements. Intracellular recording from rostral medullary inspiratory neurons revealed that DHD, like SKF-38393, increases and prolongs inspiratory phase membrane depolarization, resulting in a longer and more intense discharge of action potentials. Remarkably, DHD had opposite effects on Aug-E neurons. Membrane potential was hyperpolarized, and action potential discharges were suppressed or abolished. In association with reduction of discharge intensity, action potential half width was reduced and after-hyperpolarization increased. The stimulatory action of DHD on inspiratory motor output is attributed to D1R effects, while the depression of Aug-E neurons seems to be linked to D2R actions on the postsynaptic membrane.

Dopamine Receptor Subtypes Mediate Opposing Effects on Form Deprivation Myopia in Pigmented Guinea Pigs

“…Specifically, D1R stimulates adenylate cyclase activity, whereas D2R inhibits it, suggesting that cAMP-sensitive responses could mediate either increases or decreases in myopia progression. Such opposing effects of D1R and D2R activation in other species are also reported to affect respiratory control, [29][30][31] licking behavior, 32 alcohol consumption, 33 etc.…”

Active Emergence from Propofol General Anesthesia Is Induced by Methylphenidate

“…In this study we did not perform plethysmography experiments during propofol general anesthesia, because unlike inhaled anesthetics, the elimination of propofol does not involve the pulmonary system. However, there is considerable evidence that activating dopaminergic neurotransmission increases respiratory drive, 24–26 so it is reasonable to predict that methylphenidate would also stimulate breathing during propofol general anesthesia. It is noteworthy that the animals in the present study inhaled room air (unlike the animals in our previous study that inhaled pure oxygen as the carrier gas for isoflurane), demonstrating that hyperoxia is not necessary for methylphenidate to induce emergence from general anesthesia.…”

Dopamine D1 receptors control exercise hyperpnoea in mice

“…Extracellular dopamine release has also been observed in the nucleus accumbens in rats during treadmill running and shows possible mesolimbic dopaminergic functions related to motivation and reward (Wilson & Marsden, 1995). In the field of respiration, the non‐selective dopamine agonist apomorphine decreased central ventilatory response to hypoxia in conscious cats (Bonora & Gautier, 1988), and a similar agonist, dihydrexidine, increased the intensity and duration of inspiratory motor output in anaesthetized cats (Lalley, 2009). Thus, dopamine is involved not only in the physical performance with psychological effects during exercise, but also in respiratory control upon environmental changes.…”