Psych Drugs and Behavior Notes Part II The Addiction Process 2 Parts 1) Chronic, compulsive use of a drug 2) Use in the face of negative consequences Three Phases of Addiction Phase 1 -A person tries a drug -Decides if they like it or not -Individual differences in response Phase 2 -More and more direct use of the drug Phase 3 -Addiction -High probability of relapse -Drug therapy doesn't work very well -Craving for the drug Tolerance -Downregulation of receptors -Occurs from continuous exposure Sensitization/Reverse Tolerance -Increase effectiveness of a drug with periodic use -Rats repeatedly given amphetamines, effects grew stronger -Possibly due to upregulation of receptors Placebo is a form of conditioning Implosive Therapy -A form of desensitization -Metabolic changes in the brain Louis Baxter -UCLA/Alabama -Both SSRIs and psychotherapy cause changes in the brain Somatic -refers to physically evident signs Physiological Addiction vs. Psychological Addiction Heroin Withdrawal -Physiologically Addictive: obvious somatic signs -Diarrhea -Cold turkey hair/piloerection Cocaine Withdrawal -no medical/physiological signs -depression -"Psychological Addiction" Food/Sex/Video Game/Gambling Addiction -characterized by compulsive use in the face of negative consequences Drugs only temporally removes craving; it's no longer pleasureable Glutamate -Major excitatory transmitter -Only one glutamate -Many glutamte receptor GLURs (Glutmate Receptors) Ionotropic -NMDA (N-methyl-d-aspartate) -AMPA -Kainate (Kainic acid) Metabotropic These chemicals don't naturally exist in the brain Light and Cocaine Conditioning -Classical conditioning -Light (CS) -Cocaine (US) -Light produces effects of cocaine (CR) Light could cause the release of dopamine Primary Reward -Unconditioned Stimulus -Good when you first try it -Sex/Food Secondary Reward/Conditioned Reward -Neutral stimulus conditioned to release glutamate LTP (Long-Term Potentiation) -Strengthening the synapse by upregulation of glutamate receptors -Last for hours, days -May be the basis for long-term memory Tetanus -Period of overstimulation NMDA Receptors -Mg++ (Magnesium ions) block the receptor -The membrane must be depolarized by another transmitter (-65mV) to (-30mV) -Mg++ is ejected -Na+ (Sodium ions) and Calcium ions rush in -Calcium causes the formation of AMPA receptors Kindling -Little seizures that lead to bigger ones -Probably caused by LTP Schizophrenic Episode -Requires antipsychotic drugs -caused by an LTP-like mechanism Tail-Flick Test -Tail on light bulb -Latency: How long until the rat flicks its tail? -Analgesics increase latency -Injection in experiment vs. home cage -More analgesia in experimental Hyperalgesia -Extreme sensitivity to pain Opiates -Narcotic analgesics -Sleep-inducing -Euphoria/Reverie Heroin -acetyl groups added to morphine -thought to have no abuse libility -more lipid soluble -95% relapse rate Morphine natural Heroin semi-synthetic Demerol synthetic opiates Percodan Darvon Dilaudid Methadone -Synthetic narcotic analgesic -Invented by the Germans -Called Dolophine -Basically gov. supplied opiates Opiate Receptor Opiate Receptor Antagonists -Nalaxone -Naltrexone 1) Is there an opiate receptor a. Solomon Snyder and Candace Pert at Johns Hopkins b. Radioactive antagonist looked at binding site c. Famous overnight 2) What acts like morphine in our body? a. Hans Hosterlitz, fleeing the Nazis, went to Scotland b. John Hughes, bioassay c. Enkephalins from the head d. Endorphins from the pituitary gland e. Dymorphins 3 Main Varieties of Opiate Receptors 1) Mu responsible for analgesia and abuse 2) Kappa 3) Sigma? Huda Akil -Electrode in the central gray of rat brain produces analgesia Endorphins -hormone/pituitary gland -related to addictive nature of running -Endorphin levels increase greatly during labor Enkephalins -neurotransmitters -related to eating sweets Belluzzi and Stein -IVSA/ICV of enkephalins -Rats self-administer -Evidence that they're rewarding Acupuncture -seems to induce enkephalins in specific ares Short Axons/Colocalized -Primary/Classical Transmitter GABA -Colocalized transmitter Enkephalins/Dymorphins Opiates in VTA will provoke dopamine release in the mesoaccumbens system by suppressing GABA Rats continue to self-administer opiates even after 6-Hydroxy Dopamine surgery on the accumbens Brain systems for reward and analgesia are separate Antidepressants Anhedonia -loss of feeling of pleasure -component of major depression DSM-IV -Diagnostic and Statistical Manual, ed. 4 -Every syndrome has a number -goal to be evidence-based Major Depressive Disorder -co-morbid with anxiety -DSM I and II, classified as either endogenous or reactive -must meet 5 of 9 symptoms for 2 weeks Symptoms 1) Depressed mood, most of the day, everyday 2) Diminished interest/pleasure 3) Significant weight loss/gain 4) Insomnia/Hypersomnia 5) Psychomotor retardation or agitation 6) Fatigue or loss of energy nearly everyday 7) Feelings of worthlessness or excessive or inappropriate guilt nearly everyday 8) Diminished ability to think or think; indecisiveness 9) Recurrent thoughts of death or suidical ideation The Hamilton Depression Rating Scale (HAM-D) is a 21-question multiple choice questionnaire which doctors may use to rate the severity of a patient's depression. It was originally published in 1960 by Max Hamilton, and is presently one of the most commonly used scales for rating depression in medical research. The questionnaire rates the severity of symptoms observed in depression such as low mood, insomnia, agitation, anxiety and weight-loss. The doctor must choose the possible responses to each question by interviewing the patient and observing their symptoms. Each question has between 3-5 possible responses which increase in severity. The first 17 questions contribute to the total score and questions 18-21 are recorded to give further information about the depression such as if paranoid symptoms are present. MAOIs (monoamine oxidase inhibitors) -MAO breaks down monoamines, thus MAOIs impairs the breakdown of dopamine, serotonin, and norepinephrine -Reversible (short-lasting) or Irreversible (long-lasting) Tyramine -usually broken down by MAO -elevates blood pressure -comes from red wine and cheese Trycyclics -impair reuptake (NE, 5-HT or both) Second-Generation Compounds 1) SSRIs -Prozac 2) Non-SSRIs -reuptake -Only Wellbutrin (bupropion) acts on dopamine Above 20K, there is no relationship between happiness and money Learned Helplessness -1960s, Solomon and Seligman at UPenn -Training dogs to escape something like electric dog -Dogs pre-exposed to inescapable electric shock failed to learn to escape Locus of Control/ Internal or External Learned Hopefulness -Positive Psychology -Dr. Keys, sociology Cognitive Behavioral Therapy -works well with depression -straight-forward -what works Controllability and Depression -Jay Weiss, trained as clinical psychologist -3 groups of cats, put into tiny chambers with a paddle wheel -Cuff electrode on tail Group A -Shock-escape -Spinning the wheel turns off the shock Group B (Depressed Group) -shock-no control -yoked to the first -Group A's spinning turns off the shock -Depression last about 72 hours -40% showed no effect Group C -no shock -wheel does nothing *Magic factor is controllability Vogel -Deprivation of REM sleep in humans is antidepressant Virtually all antidepressants suppress REM sleep DSM Criteria: Either Psychological or Behavioral Rat Tested for Depression -Can be tested for behavioral criteria of depression: anhedonia, interest, sleep Mirmiran -left Iran, went to the Netherlands -Research on sleep -REM sleep greater at youth -95% in Utero REM sleep -suppressed REM in young rats, for 2 weeks after birth, showed more REM than normal Normal rats don't drink alcohol Clomipramine rats drink alcohol Stress in People and Uncontrollable Stress in Rats lead to Depression ICSS (Intracranial Self-Stimulation) Zacharko -Protection of Accumbens ICSS from Acute Stress by DMI -Head-dip/Brain Stimulation of accumbens -Stress = Foot Shock Four Groups 1) Saline/No Shock Response Rate About Same 2) Saline/180 Shocks Plummetting/Anhedonia 3) DMI (Human antidepressant) Bounced Back 4) DMI/No Shock Normal, no consistent increase, doesn't elevate response // Criticism: Shock is PTSD Antidepressants -don't work for weeks -no abuse liability -protect you from stress //3 Drugs Everyone Should Take 1) Aspirin -Prevents blood clots -Anticancer 2) Beta-blocker -heart rate down 3) SSRIs -Stress in short period of time (PTSD) -More for Anxiety disorder than depression Moreau/ Protection of VTA ICSS