PSYCH 265 1st Edition Lecture 18Outline of Last Lecture I. Ethanol action at GABA(A) Chloride Channel receptor complexII. Ethanol action at NMDA receptorIII. Central effects of ethanolIV. Enzyme inducing effects of ethanolV. Endocrine effects of ethanolVI. Gastrointestinal effectsVII. Synergistic CNS depressionVIII. Effects on liverIX. Effects on immune systemX. Effects on nervous systemXI. Alcohol related cancersXII. Tolerance Outline of Current Lecture I. Dependence on ethanol II. Withdrawal from ethanol a. Minor b. Major III. FASDIV. FASV. Characteristics of FASVI. Behavioral characteristics of FASVII. Brain anomalies in FASVIII. Pharmacokinetics of morphine IX. Opioids receptor X. Analgesic effect XI. Hyperalgesic effectXII. Behavioral effects of morphine`Current Lecture-Dependence on Ethanol oDopaminergic neurons in the VTA that project to the nucleus accumbens (Nac) are undertonic inhibition by GABAergic interneuronsoGABA release from these neurons is, in turn inhibit by mu-opiod receptors (MOR)These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.oWhen alcohol ingested, endogenous opioids such as beta-endorphin (B-EP) are released,resulting in inhibition of GABA release in VTA and removal of inhibitory tone from the dopamine cells oThis cascade results in increased dopamine release in the terminal areas in the Nac -Withdrawal from ethanol oMinor withdrawal Little or no disorientation, tremor, perspiration, hallucinations, convulsions oMajor withdrawal (delirium Tremens) Profound disorientationTremor, profuse perspirationIncreased Autonomic activity Increased psychomotor activity HallucinationsAbsence of convulsionsPossible death from respiratory failure & cardiac arrhythmias -Fetal Alcohol Spectrum Disorders (FASD)oFASD is broad range of effects & symptoms caused by prenatal alcohol exposureFetal alcohol syndrome (FAS)Partial fetal alcohol syndrome Some but not all signs of full FASAlcohol related birth defects (ARBD)Heart, kidney, bone and sensory problems Alcohol related neurodevelopment disorders (ARND)CNS abnormalities and/or cognitive & behavioral problems -Fetal Alcohol Syndrome (FAS)oMost serious consequence of heavy drinking during pregnancy oLargest cause of non-hereditary mental retardation in USoEstimated prevalence 60 per 1000oEstimated incidence of 0.5-2.0/1000 live births -Physical characteristics of FASoPattern of facial abnormalities including wide set of narrow eyes, smooth ridge on upperlip, thin upper lip borderoGrowth defects both prenatally & after birth oCNS abnormalities oCan also have Smaller than average size brains Coordinated problems Abnormal formation of bones and some organs Reduced immunity -Behavioral Characteristics of FASoMay have difficulty in Learning & remembering Understanding & following directionsShifting attention Controlling emotions & impulsivity Communicating & socializing Practicing daily life skills, including feeding, bathing, counting money, telling time, and minding personal safety -Brain anomalies in FASoMicrocephaly oAbnormal corpus callosum MORPHINE -Pharmacokinetics of morphine oMedical purposesIV injection is most common method of administration oSubject to extensive first-pass metabolism Taken orally 40-50% of dose reaches CNS oAlso taken orally, sublingually, subcutaneously, brutally, rectally, intranasally, intravenously, intrathecally or epidurally, or inhaled via nebulizeroOn streets it it is becoming more common to inhale (chasing the dragon)oMetabolized primarily in live & 87% of dose is excreted in urine within 72 hr of administration oPrimarily conjugated to glucuronic acid & resulting in morphine-3-glucuronide (60% inactive metabolite) and morphine-6-glucuronid (6-10% active metabolite) oGlucuronides excreted in urine & feces-Opioids Receptor oPrototype opioids analgesic, morphine has affinity and efficacy for the mu-opioid receptor oMu-opioid receptor is a metabotropic receptor coupled to g-protein oOpioids decrease chronic dull pain more than acute sharp pain but sufficient dose can decrease any pain oOpioids generally used to treat moderate-to-severe pain -Analgesic Effect of morphine -Morphine activation of opiate receptors decrease substance P (and probably glutamate) neurotransmission in the primary pain pathway-Hyperalgesic effect of morphine -New problem in the treatment of chronic pain -Behavioral effects of morphine oSedation oEuphoria Stimulation of dopamine in reward centerInitial doses lead to euphoria but at higher doses unpleasant symptoms as delirium hallucination, dizziness and confusion oRespiratory depression Decreased sensitivity of respiratory center in Medulla Oblongata to