Psyc4130 1nd Edition Lecture 36 Outline of Last Lecture I. VTAII. Hedonics ModelsIII. Self-MedicationIV. Brain PlasticityV. Who Becomes Addicted?VI. PFC UnderdevelopmentVII. ToleranceVIII. WithdrawalIX. Withdrawal and Neg. Reinforcement Outline of Current Lecture I. SSRI Synaptic ActionII. SSRI Side EffectsIII. Serotonin SyndromeIV. SSRIs and Pediatric Psychiatry V. Trazodone (Desyrel)VI. SNRIsVII. Bupropion (Wellbutrin)VIII. Efficacy of Antidepressants IX. Do Happy Pills Work?X. Addiction- Withdrawal & Neg ReinforcementXI. Review Current Lecture SSRI Synaptic Action- More recent research has demonstrated that augmenting 5-HT1A receptor activity leads to the therapeutic effects of SSRIs.- Many of the side effects are mediated through enhanced 5-HT2 receptor activity. SSRI Side Effects- Less toxic/dangerous/severe Serotonin Syndrome- Rare but toxic!!- Disorientation/Confusion w/ Possible Mania-Severe Psychomotor AgitationThese 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.- Severely Elevated Blood Pressure-Fever/hyperthermia- Cold Sweats (Diaphoresis)- Diarrhea- Visual Disturbances-Coma and Possible death SSRIs and Pediatric Psychiatry- Some mid-2000s reports indicated an increase risk of suicide ideation and behavior in youth taking SSRIs.- Due to media attention and FDA warnings, prescriptions dropped precipitously.o Physicians less likely to prescribe drug- Since then, there is evidence that suicide rates among young people in the US are increasing. Trazodone (Desyrel)- A modified SSRI- Blocks 5-HT RI (i.e. blocks 5-HT transporter)o antagonist- Blocks 5-HT2A receptors postsynaptically (minimizes side effects) SNRIs- Block reuptake of NE and 5-HT with fewer non-specific actions than TCAs - Venlafaxine (Effexor)o RI of NE and 5-HT - Duloxetine (Cymbalta)o RI of all three monoamines Bupropion (Wellbutrin)- “Atypical” Antidepressanto Dopamine reuptake inhibitor, selective (like an SDRI)- Does not significantly influence 5-HT activity- Mechanisms of Action: DRI, Partial NERI, Antagonizes nAChRso Smoking cessation- antagonization - Equal antidepressant efficacy vs. SSRIs- May actually increase libido; therefore, bupropion may be used in conjunction with SSRIs. - Has psychostimulant properties, but not addictive (like cocaine or amphetamines), due to slow absorption and reduced transporter occupancy- Side Effects: Restlessness/Agitation, Motor Tics, Tremors, decrease Appetite (and Weightloss), GI Disturbance, Seizures (Rare)- Contraindicated in patients with panic disorder, epilepsy or other seizure disorders Efficacy of Antidepressants - Variable!!o Relatively week overall clinical efficacy- Up to half of all patients do not respond to initial pharmacotherapy.- Some of these, however, will respond to a different antidepressant.- Among responders, some experience decreased efficacy (“Poop Out”) over time. o Drug becomes less and less effective over time Do Happy Pills Work?- Kirsch and Sapirstein (1998) analyzed results from 19 clinical studies and estimated that the vast majority of the effects of prescription antidepressants owed to classic placebo/expectancy effects. - They suggested that most of the remaining effects owed to “active placebo” effectso Placebo effects, increasing serotonin transmission, gets effects, but not exact effects that would/should help aka bodily change makes you think its working Addiction- Withdrawal & Neg Reinforcement (chapter 18)- Relapsing into drug abuse to keep negative withdrawal effects at bay- Aversive withdrawal, make it goes away = reuse- Tends to maintain, & reinstatement/relapse- Relapse/reinstatement can be primed or cued (environmental context)- GABA activity in the dorsal ACC appears to intensify drug cravingo Triggers response in reinforcement apparatus in the brain- The dorsal ACC has excitatory connection to the VTA- Administration of a GABA agonist therefore decreases reinstatement by reducing VTA activity - On the other hand, activity in the vmPFC inversely relates to relapse/reinstatement - Chronic use of cocaine is associated with 5-11% loss of grey matter in various regions of the PFC- Other researchers have substantiated losses of PFC and limbic cortex gray matter in chronic users of cocaine and methamphetamine (Thompson et al., 2004; Ersch et al., 2011) and a decrease in mPFC activation in heavy smokers and pathological gamblers (de Reuiter et al., 2011)- Addiction = BAD for PFC- Stress can both predispose substance abuse/addiction and TRIGGER relapse/reinstatement - Maternal deprivation- rats, take mom away from babies for an hour a day, test when they are adults, (stress/anxiety)- Social defeat- induce a naturalist type of stress in animals - Know CRH for final ***o Only hormonal pathway, fight or flight responseo Administering CRH can reinstate drug taking behavior- Partial agonists can help reduce cravings- Buprenex- partial agonist, working as an antagonist Review- Schizo and depression (know transmitter hypothesis), how research led to a revisiono Dopamine hypothesis, original one and how it was revised - 50-100 questions multiple choice- 70% on newer stuff since emotions- AIS/CAH (sex hormones)- mix
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