Drugs and Brain Mid Term 2.docx

1 Drugs and Brain Mid Term 2 CHAPTER 5: DRUGS OF ABUSE -One of the first national regulations on drugs of abuse= Harrison Narcotics Act 1915 -U.S Drug Enforcement Administration (DEA) uses 5 schedules to categorize drugs of abuse the lower the schedule number (sched 1,2..) the greater potential for abuse Schedule I Heroine, LSD, Marijuana (high abuse potential; no legitimate medical uses) II Cocaine, Morphine, Phencyclidine (PCP) (high abuse, legitimate medical uses) III Ketamine IV Aplrazolam (Xanax) V Codeine *criticism of controlled substances: appropriateness od drug 2) methods used to schedule drugs CLINICAL DEFINITIONS AND THE DIAGNOSIS OF DRUG ADDICTION • The DSM provides a clinical definition of drug addiction and substance abuse Drug addiction characterized by: - substance dependence: maladaptive pattern of substance abuse (impairment or distress as manifested by 3 or more symptoms at any time in the same 12 month period).. symptoms= tolerance, withdrawal, taking time to use and look for drug – Substance abuse: maladaptive pattern of substance use that does not involve tolerance or dependence (impairment or distress manifested by 1 or more symptom occurring within a 12 month period) – Relapse: return to a chronic drug use state that meets the clinical features of addiction THEORETICAL MODELS AND THE FEATURES OF DRUG ADDICTION • Drug -addiction models attempt to characterize and explain compulsive drug use 1) Disease Model of Drug Addiction -characterizes drug addiction as a disease – How do drugs of abuse interrupt, cease, or disrupt neurobiological processes? – Substance (drug) serves as the cause of the disease (addiction) – People may have a predisposition for drug addiction 2) Associative Learning Principles • Associative learning: making associations between stimuli or behavior and stimulus – Based on principles of operant conditioning and classical conditioning -– Associative learning occurs during certain conditions or environmental contexts Operant conditioning: behavior occurs as a result of meeting past consequences – Reinforcement: consequences of response increases frequency of future 2 responses – Conditioning: a stimulus acquires the behavioral effects of another stimulus Classical conditioning: developing associations between neutral stimuli and those stimuli that produce natural reflexes –->Unconditioned stimulus (UCS) evokes a natural response, termed unconditioned response (UCR) –-> Repeated pairing of a neutral stimulus with UCS causes neutral stimulus to become a conditioned stimulus (CS) This pairing yields a conditioned response (CR) *conditioning may also occur for motivational states: • Incentive salience: attribution of salient motivational value to otherwise neutral stimuli – These attributions occur through associations of neutral stimuli with rewarding stimuli -important for modern drug addiction theory: neutral stimuli assoc w drug use makes person search out for drug *we also have goal directed behaviors important in decision making • Goal-directed behavior occurs when an organism engages in learned behaviors in order to achieve a desired goal 3) Drive, Opponent-Process Theory, and Incentive-Salience Models • Drive theory (Wikler): drug-addicted individuals develop a drive to achieve a drug’s positive reinforcing effects • Opponent-process theory (Solomon and Corbit): effects of a drug are automatically counteracted by opposing actions in the body ..these actions serve to attain homeostasis ..if add more than normal amount of drug we get an effect, if stop then we get withdrawal • Incentive-salience: drug addiction occurs after a shift from “liking” the effects of a drug (enjoying effects; not drug addiction) to “wanting” the effects (occurs in incentive salience; you are motivated; drug addiction) Box 5.1 Self-Administration -Measure a drugs reinforcing strength by its breaking point (max amount of response effort an organism will devote towards receiving an administration of drug) DRUGS OF ABUSE AND REWARD CIRCUITRY • Acute administration of drugs of abuse produces reinforcing effects by activating reward circuitry • Key structures of reward circuitry (figure 5.3) : – Ventral tegmental area (VTA): contains soma of dopamine neurons – Nucleus accumbens: brain area in which VTA dopamine neurons project to and terminate in *this is where reinforcing effects occur -Many drugs of abuse cause dopamine elevations far above those produced by natural reinforcers -Some drugs of abuse indirectly alter dopamine neurons by acting on other 3 neurotransmitter systems (like GABA; released from VTA activate GABA receptors on dopamine neurons, it decreases activity of dopamine neurons and reduces dop levels in nucleus accumbens..then gaba in nucleus acc project to VTA ) DRUG ABUSE AND CHANGES TO LEARNING AND MEMORY SYSTEMS • Chronic administration of drugs of abuse leads to changes in brain systems involved in learning and memory – Amygdala: assoc stimuli commonly present during drug use w emotional events ex reinforcing effects from a drug.. amyg connects to : – Thalamus: routes sensory info to the cerebral cortex – Prefrontal cortex: stimuli processed and motor responses are initiated (orbito important for drug cravings and incentive value) *together forms thalamo-cortical-amygdala pathway – Hippocampus: connects with thalamo… provides contextual info linked with the drug taking (ex environment where drugs are normally taken or types of ppl the person interacts w when taking drug) NEUROBIOLOGYAND THE STAGES OF DRUG ADDICTION • Addiction is a cycle involving three primary stages: – Intoxication acute drug effects; neurobiology= reward circuitry – Withdrawal repeated drug use results in physical or psychological withdrawal effects; neurobio= amygdala, hypothalamus, and autonomic nervous system – Preoccupation and anticipation behavior orients from seeking natural reinforcers to seeking drug reinforcers; neurobio= prefrontal cortex, amygdala, thalamus, hippocampus THERAPIES FOR TREATING DRUG DEPENDENCE • Drug-addiction treatment options include psychotherapy, medications, or both – Addresses drug detoxification, coping with withdrawal symptoms, and preventing relapse • Intoxication: drug’s acute maladaptive or impaired effects • Detoxification: ceases drug intoxication and reduces withdrawal symptoms • After drug detoxification, goal is to reduce further withdrawal symptoms and drug cravings and to prevent relapse – Medications: to reduce short-term withdrawal symptoms… address withdrawal, comorbid disorders, drug-replacement therapy (exchange addictive drug w similar but less harmful drug), and/or cravings – Psychotherapy: include behavioral therapies, cognitive–behavioral therapies, and social therapies CHAPTER 6: PSYCHOSTIMULANTS PSYCHOSTIMULANTS: A LARGE VARIETY OF SUBSTANCES • Psychostimulants/ sympathomimetics: increase psychomotor and sympathetic nervous system activity as well as improve alertness and positive mood • Common psychostimulants: – Amphetamines 4 – Methylphenidate – Cathinones – Cocaine PSYCHOSTIMULANTS: HERBAL REMEDIES, PRESCRIPTION DRUGS AND SUBSTANCES OF ABUSE • Ephedra: – First amphetamines were derived from ephedra – Contains two psychoactive components: ephedrine and pseudoephedrine – Many cold remedies contain these stimulants -U.S. pharmacies regulates sales to reduce production of methamphetamine Amphetamines • Amphetamines: class of psychostimulant drugs that share a similar structure -has two optical isomers (chemical structure occurs in 2 diff forms that are mirror images of each other- designated as d or l) • Methamphetamine (Desoxyn): synthesized from ephedrine, pseudoephedrine, or the organic solvent phenylacetone – Meth labs produce crystallized form (household chemicals w either ephedrine or pseudo) referred to as: crystal meth, crystal, speed, or crank Methylphenidate • Methylphenidate: prescription psychostimulant drug used to treat ADHD – Weak psychostimulant drug – Recreational involves grinding up drug and snorting it (Referred to as kiddie coke) Cathinones • Cathinone: psychostimulant derived from the leaves of Catha edulis, also referred to as khat – Found in east Africa and the Arabian Peninsula • Derivatives of cathinone used as psychostimulants: Methcathinone, methadrone, and pyrovalerones Cocaine •Cocaine: derived from the leaves of erythroxylon coca - (Clandestine cocaine processing) Coca paste: liquid paste from the breaking and mixing of coca leaves (contains 30-80% of cocaine bases) - Crystal labs convert cocaine from bases into high purity salt that can be insufflated (snorted) or injected -Freebase: heating (from baking soda and water) and smoking the freebase form of cocaine (termed crack) *users prefer base form b/c it has lower temp point to allow to easily smoke it (salt form has higher temp but is more safely to inhale) INSTRUMENTALAND RECREATIONAL PURPOSES OF PSYCHOSTIMULANTS • Amphetamines: – 1887: developed as mass producible form of ephedra – World War II: used to improve alertness and reduce fatigue – 1919: introduction of methamphetamine production – 2006: the DEA begins regulating the sale of ephedrine and pseudoephedrine 5 • Methylphenidate: – 1944: discovered by Leandro Panizzon – 1960s: prescribed for the treatment of ADHD • Methcathinone: -first documented cultivaton of khat in 1300s – 1760: methcathinone introduced to Europe – 1970s: recreational use begins – 1990s: reports of methcathinone use begin • Cocaine: – Erythroxylon coca: long used by indigenous people for religious purposes, appetite suppression, and enhanced vigor and stamina – 1844: cocaine first extracted from coca leaves – 1884: Freud publishes Über Coca • Freud first lauded the benefits of cocaine • Freud later declared cocaine a “scourge” of humanity PSYCHOSTIMULANT ADMINISTRATION • Routes and forms of psychostimulant administration – Therapeutic usage: oral administration in pill or liquid form – Reinforcing effects: intravenous injection, insufflation, and inhalation • Salt forms allow for intravenous injections salt necessary b/c drugs must be water soluble for proper absorption through membranes • Base forms allow for inhalation  smoking freebase cocaine can release methylecgonidine (harmful for lungs heart and liver) *Volkvow : inhalation of cocaine @ peak= 1.4 min; intraveneous= 3.1 min; insufflation= 14.6 min PSYCHOSTIMULANTS AND MONOAMINE NEUROTRANSMITTERS • Amphetamines: Increase synaptic dopamine levels through two mechanisms of action: 1) Amphetamine & methamphetamine Expels dopamine from neuron (through dopamine membrane transporters causing reversal in the direction of the dopamine transporter) and 2) prevents dopamine storage (by entering dopamine storage vesicles through the vesicular transporter and displacing dopamine from the vesicle) *Figure 6.8 • Methylphenidate: – Prevents reuptake of dopamine, serotonin, norepinephrine and blocks dopamine storage in synaptic vesicles • Cathinone: – Reduces reuptake of dopamine, norepinephrine, and serotonin *Baumann: elevated concentrations of these neurotrans occurred in nucleus 6 accumbens methyl & mepe reduced reuptake of dopamine, norep and serotonin; both had weaker potency than methamphetamine on dop and norep reuptake as well as weaker on dopamine and norep release.. methamp & mepth similar potency for serotonin • Cocaine – Prevents reuptake of dopamine, norepinephrine, and serotonin -NA+ blocker channel at high doses • Cocaine- and amphetamine-regulated transcript (CART) - Peptide neurotransmitter produced after psychostimulant administration -Increases dopamine release Figure 6.10 PHARMACOLOGICAL EFFECTS OF PSYCHOSTIMULANTS Physiological Effects • Activation of sympathetic nervous system – Increased heart rate – Constriction of blood vessels – Relaxed airways – Dilates pupils – Inhibits salivation and digestion • Accounts for many of the uses and risks associated with psychostimulants (ex remedy in colds= ease nasal congestion & open airway in lungs; hypothermia, suppress appetite called anoretics by hypothalamus) Behavioral Effects • Increase in purposeful behavior (low dose) – Fast speech; faster completion of tasks – Rate-dependency : reflect differences in a drugs behavioral effects as a function of predrug administration response rates (they increase low rates of baseline behavioral activity & decrease high rates of behavioral activity.. ex amphetamine increased activity in rats that has low rates of lever pressing; amph decreased activity in rats that had high rate of pressing) • Increase in purposeless behavior (high dose) – Stereotypy (nonhuman purposeless behavior): repetitive grooming, head swaying, gnawing, licking – Punding (human purposeless behavior): teeth grinding, tapping, skin picking, or nail biting Subjective Effects • Low dose effects – Increased energy – Alertness – Sense of well-being – Enthusiasm • High dose effects – “Rush” – Euphoria 7 Johanson: break point (assesses strength of positive mood effects of drug) is highest for d amphetamine and methamphetamine where cocaine lowest; rats willing to work harder for d amph and meth than for coke Adverse Effects • Physiological: – Pulmonary dysfunction (injury during inhalation, tissue inglamation) – Abnormal fetal development – Tooth decay (meth mouth= chemical, not brushing, sympathetic nervous system [reduces salivation & therefore makes thirsty but they drink soft drinks so sugar]) – Risk of infection • Psychosis: Paranoia ,Agitation, Hallucinations like schiz but diff b/c drug halluc are tactile (ex crawling bugs.. schiz don’t hallucinate that) & visual + olfactory halluc (schiz is auditory) PSYCHOSTIMULANT DRUGS PRODUCE SENSITIZATION AND TOLERANCE • Sensitization occurs for purposeless behavior – Incentive sensitization • Tolerance occurs for positive subjective effects -pharmopsychodynamic tolerance: changes in dopamine D2 receptor sensitivity -cross tolerance btw psychostimulant drugs Figure 6.13 From Actions to Effects: Psychostimulant Addiction • Linking pharmacological actions to reinforcing effects – Reinforcing effect due to increased dopamine neurotransmission in nucleus accumbens – Withdrawal symptoms primarily occur from psychological dependence • Genetics influence the susceptibility to psychostimulant addiction: -P450 enzymes leads to quicker metabolism, therefore creates shorter drug effect and leads person to use more -genetic predisposition can increase effects of drug leading to more use -genetic predisposition can create negative effects making drug addiction unlikely -C-1021T polymorphism gene: low expression of dopamine B-hydrox (enzyme converts dopamine to norep).. may increase negative effects of drugs • Treatments for psychostimulant addiction: – Disulfiram : meds treating alcohol addiction that inhibits aldehyde dehydrogenase (reduces positive effects) – Modafinil (provides safe substitute for abused psychostimulant drugs) – Tricyclic antidepressants (reduce cravings, depression & other withdrawal symptoms) – Topiramate (cocaine relapse prevention) – Vaccinations (prevent drug from crossing blood-brain barrier) CHAPTER 7: NICOTINE AND CAFFEINE NICOTINE: KEY PSYCHOACTIVE INGREDIENT IN TOBACCO 8 • Nicotine: central psychoactive ingredient in tobacco •