Neuromodulation 2 Flashcards
What are hippocampal theta waves?
Theta waves have activity across the hippocampus – if have glutamate release in coincidence with the release of this, LTP can occur. These theta waves set up in the hippocampus how learning and memory can occur. Wave form could be controlled by acetycholine release into the hippocampus. Release comes from one place in the brain, but has wide distributions. See how you get a pattern of behaviour across the brain.
Scopolamine = antagonist that shows these waves are controlled by acetylcholine.
What is the opioidergic system?
Endogenous opioids = products of DNA being transcribed into proteins which are made into neuropeptides, and these hit opioid receptors in the brain. Agonists = opiates e.g. morphine & heroin. Antagonists = naloxone & naltrexone - given to people who have taken a heroin overdose, which block the action of the opioid at the receptor. Too much activation of these receptors can lead to highly negative symptoms e.g. respiratory failure.
What are the effects of morphine and heroin?
Drugs both act at the same receptor. Same substrate on the receptor. Different effects are due to the rate that it gets into the brain and across the blood/brain barrier. Heroin does this faster.
After repeated use the system adapts itself to become used to the drug – therefore need an increased dose to get the same feeling. This is due to compensatory changes in the pathways. Changes in the cascade are thought to cause the effects of tolerance.
What happens in the regulation of firing of noradrenergic neurons in the Locus Coeruleus
Sustained release of noradrenaline leads to activation of the autonomic nervous system. Opioids oppose the actions of noradrenaline = more relaxed state. Firing of the cells in the locus coeruleus are regulated by opioids. Think this is what produces the calming effect of opioids.
What is the action of opiates on LC firing?
Chronic activation of opitate receptors leads to tolerance to drug effects. Homeostatic mechanism compensating for the functional changes. Withdrawal systems are due to overactivation of the autonomic nervous system.
How does tolerance to opiates occur?
Chronic activation of opiate receptors leads to homeostatic mechanism that compensates for the functional changes leading to tolerance and physical dependence. Acute morphine - acutely inhibits firing of LC neurons through Gi pathway. Chronic treatment - LC neurons return to their normal firing rates. Withdrawal - dramatic increase in LC firing.
What happens due to acute morphine exposure?
Acutely inhibits firing of LC neurons. LC cell inhibited (cannot fire). Down-regulation of arousal system = relaxed feeling.
What happens due to chronic morphine exposure?
System wants to normalise to get back up to normal firing levels. The process that gets the LC to firing normally is an upregulation – amount of adenylyl cyclase gets upregulated. More proteins to be activated, which means everything returns to normal levels. cAMP pathway function restores to normal levels. Tolerance = need to increase dose of morphine to provide equivalent inhibition.
What happens due to withdrawal?
All things stay upregulated. When take morphine away loose GI signal, and then as a result if there’s any stimulatory action, it will activate what was inhibited, more PKA and have a much bigger action (phosphorylate all proteins), firing lots of action potentials. Before sodium was being inhibited, now got an influx of sodium into cells. Get LC firing increase above normal levels. This results in the autonomic affects associated with physical withdrawal.
How to opiate withdrawal syndrome and fight/flight response compare?
Some symptoms of opiate withdrawal syndrome are anxiety, restlessness, insomnia, and loss of appetite. Can therefore be said that symptoms of opiate withdrawal are an extreme version of the fight/flight system.
