PSYCH 634 Week 1 Neurons and Neurotransmission Example

Why Opioids Slow Breathing During Sleep: Neurons, Receptors and Naloxone Explained Through One Sleep Study

[Student Name]

University of Phoenix

PSYCH/634: Biological Basis of Behavior

Week 1 Assignment

[Instructor Name]

[Date]

The sleep lab, technologist and patient are composites written for a model paper; neuroscience and clinical findings come from the sources listed.

Behavior depends on communication among billions of neurons. Understanding that communication explains how drugs change thoughts, feelings and bodily functions. This paper explains neurons and neurotransmission through a case from my work in a sleep laboratory.

What I Saw

I am a registered sleep technologist at a sleep center in Tucson, Arizona. One night I monitored a fifty-eight-year-old man referred for snoring and daytime sleepiness. He takes oxycodone daily for chronic back pain after a work injury. Within an hour of falling asleep, his breathing became irregular, and then he stopped breathing for twenty to thirty seconds at a time, dozens of times an hour. Unlike the obstructive apnea I usually see, where the chest and abdomen strain against a blocked airway, his chest did not move at all. His brain was simply not sending the signal to breathe. To understand why, I had to start with the neuron.

How Neurons Signal

A neuron receives signals through its dendrites and cell body, integrates them and, if the combined input is strong enough, sends a signal down its axon. At rest, the inside of the neuron is negatively charged relative to the outside, about seventy millivolts, maintained by ion pumps and channels. Incoming signals nudge this voltage up or down. Once the axon's starting segment is pushed past its trigger point, gates on sodium channels swing open, positive ions flood inward and for about a millisecond the inside of the cell turns positive. Potassium channels then open, restoring the negative charge. This rapid spike, the action potential, travels down the axon without weakening, much like a flame moving along a fuse.

At the axon terminal, the arriving action potential opens calcium channels. Calcium entry causes small sacs called vesicles to fuse with the membrane and release neurotransmitter molecules into the synapse, the narrow gap between neurons. These molecules bind receptors on the receiving neuron, changing its voltage or its internal chemistry. The signal ends when transmitters are broken down, taken back up into the terminal or diffuse away.

Excitation, Inhibition and Receptors

Some neurotransmitters, such as glutamate, mostly excite the receiving neuron, making an action potential more likely. Others, such as GABA, mostly inhibit it. Whether a transmitter excites or inhibits depends on the receptor it binds. Ionotropic receptors are channels that open directly when a transmitter binds, producing fast effects. Metabotropic receptors activate proteins inside the cell, producing slower and longer-lasting changes, such as opening potassium channels that make the neuron harder to fire.

Glia and the Support System

Neurons do not work alone. Glial cells, once thought to be mere packing material, insulate axons with myelin, which speeds conduction, regulate the chemical environment around synapses and clear away excess transmitter. Astrocytes help control the concentration of glutamate and potassium in the space around neurons, which affects how easily those neurons fire. Microglia act as the brain's immune cells and have been studied for their possible role in opioid tolerance and in chronic pain itself. For a patient with years of back pain, changes in glial activity in the spinal cord may be part of why his pain persists and why opioids lose some of their effect.

The Body's Own Opioids

The brain makes its own opioid-like chemicals, including endorphins and enkephalins, which bind opioid receptors. The mu opioid receptor is a metabotropic receptor. When activated, it reduces the release of transmitter from the sending neuron and makes the receiving neuron less excitable by opening potassium channels. These effects reduce pain signaling in the spinal cord and brain, which is why opioid drugs relieve pain.

Drugs that bind a receptor and activate it are agonists; oxycodone, morphine and fentanyl are mu receptor agonists. Drugs that bind without activating, blocking the receptor, are antagonists. Naloxone is a mu antagonist.

Why Breathing Slows

Breathing is generated automatically by networks of neurons in the brainstem. Pattinson (2008) reviewed how opioids affect the control of respiration. A cluster of neurons in the medulla, the preBötzinger complex, generates the basic breathing rhythm, and other brainstem areas adjust breathing in response to carbon dioxide levels. These neurons carry mu opioid receptors. When opioids bind, the rhythm-generating neurons fire less, breathing slows and becomes irregular and the brain's response to rising carbon dioxide is blunted, so the usual drive to breathe harder when carbon dioxide builds up weakens. Pattinson noted that these effects are greatest during sleep, when the conscious drive to breathe is absent.

On the monitor, the flat line on the chest belt was a cellular event: potassium channels opening on neurons that set the rhythm of breathing.

Evidence From the Sleep Lab

Walker et al. (2007) compared sleep studies of patients taking chronic opioids with matched patients not taking opioids. Central sleep apnea, pauses in breathing without effort, was far more common among opioid users, and its severity increased with the daily dose. The study confirmed in clinical settings what the neuroscience predicts and suggested that patients on long-term opioids should be screened for breathing problems during sleep.

Tolerance Develops Unevenly

Patients on long-term opioids develop tolerance, needing higher doses for the same pain relief. Volkow and McLellan (2016) reviewed misconceptions about opioids in chronic pain and explained that tolerance to pain relief and euphoria can develop relatively quickly, while tolerance to respiratory depression may develop more slowly or incompletely. This mismatch is dangerous: a patient who increases the dose to regain pain relief may push breathing suppression beyond safe levels. They also distinguished physical dependence, which develops in anyone taking opioids long term, from addiction, a pattern of compulsive use despite harm.

How Naloxone Reverses the Effect

Naloxone binds mu receptors more tightly than most opioids but does not activate them. When given, it displaces the opioid from the receptors, and the neurons that generate breathing resume normal firing. Because naloxone wears off faster than many opioids, breathing suppression can return, which is why people who receive naloxone for an overdose need continued monitoring.

Other Drugs That Add to the Risk

Opioids are not the only drugs that suppress breathing. Benzodiazepines, such as those prescribed for anxiety or sleep, enhance the effect of GABA at its receptors, increasing inhibition throughout the brain, including in breathing circuits. Alcohol acts on several systems, including GABA receptors. When these substances are combined with opioids, their effects on breathing add together, which is why such combinations appear so often in overdose deaths. Our patient's medication list included a muscle relaxant with sedating effects, which his physicians reviewed as part of his care.

What Happened Next

The patient's sleep physician reviewed the study, discussed it with his pain specialist and began treatment with a device that supports breathing during sleep. His pain specialist planned a gradual reduction in his opioid dose, combined with physical therapy. The patient also received a naloxone prescription for home.

Conclusion

A sleep study revealed what neurotransmission looks like when a drug alters it. Neurons signal through action potentials and transmitters, receptors determine the effects, and opioid agonists acting on brainstem neurons reduce the drive to breathe, especially during sleep. Understanding these steps explains both the danger of opioids and how naloxone reverses it.

References

Pattinson, K. T. S. (2008). Opioids and the control of respiration. British Journal of Anaesthesia, 100(6), 747-758. https://doi.org/10.1093/bja/aen094

Volkow, N. D., & McLellan, A. T. (2016). Opioid abuse in chronic pain: Misconceptions and mitigation strategies. New England Journal of Medicine, 374(13), 1253-1263. https://doi.org/10.1056/NEJMra1507771

Walker, J. M., Farney, R. J., Rhondeau, S. M., Boyle, K. M., Valentine, K., Cloward, T. V., & Shilling, K. C. (2007). Chronic opioid use is a risk factor for the development of central sleep apnea and ataxic breathing. Journal of Clinical Sleep Medicine, 3(5), 455-461. https://doi.org/10.5664/jcsm.26908