Morphine is the compound extracted from opium difference between heroine and morphine heroine gets through BBB faster becomes morphine in the brain 6 in 1000 2009 hospital births have opiate withdrawals oxyContin orally is slow crush it and inject can get high faster each pill has a lot in it Opioid Binding Receptors saturation of the receptors once hitting B max there are no more receptors to bind too U receptors main for how morphine works inhibits G protein inhibit cAMP humans make opiates in body made from other precursor for other cycles these originate in cytoplasm comes from pro peptides which is made from transcription POMC makes the opiate and ACTH helps pain regulation ACTH responds to stress Proenkephalin prodynorphin PO FQ differ in first molecule Hypothalamas CRF from pituitary ACTH functions analgesia reinforcement feeding cardiovascular depression antitusive vomit functions analgesia reinforcements cog function dysphoria analgesia temp control water balance feeding NE function spinal analgesia suprasinal pronociception feeding learning motor functions Receptors Endomorphins U receptors Enkephalin g receptor Dynorphine K receptor Nociceptin orphanin Inhibitory decrease cAMP postsynaptic inhibition open potassium channel axoaxonic inhibition close CA2 channels Presynaptic autoreceptors decrease release of NTs peptides are co released with other NTs Dendrite connects to skin axon connects from cell body to spinal cord release of substance P goes into the spinal cord pain afferent releases substance P neuron in the spinal cord goes to the brain to convey pain signal enkephalin is axoaxonic inhibits substance P release through calcium influx pain signal is diminished Modality specific sensory representation of physiological condition of the body Pain Pathway Pain Pathway Autonomic spinal cord VMpc thalamus interoceptive cortex insula sensorimotor cortex Area 3a Homeostatic and emotional brain stem NE parabranchial nucleus MDvc thalamus Anterior cingulate Amygdala Later pain is in anterior cingulate cortex Systems in the brain diminish the brain PAG responds to opiates excitatory situation which excites nucleus raphe which goes to the spinal cord really quick responses to pain spinal cords medulla pons effects of opiates acute action and withdrawal signs withdrawal signs are exact opposite The original opponent process molecule Tolerance to an environment is possible OD major effect of morphine and tolerance block glutamate receptor use learning mechanisms to change collaterals coming off of fiber systems that interact with local areas on the way a lot through the dopamine system but a lesion to dopamine there is still reinforcing properties Dynorphin diminishes dopamines fire rate goes down dysphoria Abuse Potential lots of DA released punishing Drug Therapy