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Neuropeptides Explained Brain Function — Comparison Across Key Peptide Classes
Opioid Peptides (endorphins, enkephalins, dynorphins) Periaqueductal gray, nucleus accumbens, amygdala, spinal cord dorsal horn (MOR), (DOR), (KOR) opioid receptors Pain modulation, reward signaling, stress-induced analgesia, addiction vulnerability Dysr
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- Opioid Peptides (endorphins, enkephalins, dynorphins)
- Periaqueductal gray, nucleus accumbens, amygdala, spinal cord dorsal horn
- μ (MOR), δ (DOR), κ (KOR) opioid receptors
- Pain modulation, reward signaling, stress-induced analgesia, addiction vulnerability
- Dysregulation implicated in chronic pain syndromes, opioid use disorder, stress-related psychiatric conditions
- Most studied neuropeptide system due to clinical relevance. Endogenous opioid tone determines both pain threshold and addiction susceptibility
- Neuropeptide Y (NPY)
- Arcuate nucleus, amygdala, hippocampus, cortex
- Y1, Y2, Y5 receptors
- Appetite stimulation, anxiety reduction, circadian regulation, stress resilience, memory consolidation
- Low NPY associated with PTSD, depression, metabolic syndrome; Y2 agonists under investigation for obesity
- Single most abundant neuropeptide in mammalian brain. Regulates both metabolic homeostasis and emotional resilience through parallel circuits
- Orexins (Hypocretins A/B)
- Lateral hypothalamus (exclusive synthesis site)
- OX1 (Hcrtr1), OX2 (Hcrtr2) receptors
- Wakefulness stabilization, motivation, reward seeking, autonomic arousal
- Orexin neuron loss causes narcolepsy; OX2 antagonists (suvorexant) used as sleep aids
- Orexins link arousal state to motivational salience. Narcolepsy patients lose wakefulness specifically during emotionally charged moments
- Vasopressin & Oxytocin
- Paraventricular nucleus, supraoptic nucleus (synthesis); nucleus accumbens, amygdala (release)
- V1a, V1b, OXTR (oxytocin receptor)
- Social bonding, trust behavior, aggression, parental care, stress buffering, HPA axis regulation
- Intranasal oxytocin studied for autism spectrum disorder, social anxiety; vasopressin implicated in aggression, pair bonding
- Differ by only two amino acids but produce opposite effects on aggression and affiliation. Receptor distribution determines behavioral output
- Tachykinins (Substance P, Neurokinin A/B)
- Dorsal horn of spinal cord, amygdala, striatum, cortex
- NK1, NK2, NK3 receptors
- Pain amplification, anxiety, emesis, inflammatory modulation, neurogenic inflammation
- NK1 antagonists developed for chemotherapy-induced nausea; substance P implicated in fibromyalgia, IBS
- Substance P amplifies glutamate signaling at NMDA receptors. Blocking NK1 reduces pain without analgesic tolerance typical of opioids