Exam 2 Study Guide Addiction A behavioral pattern of drug use characterized by overwhelming involvement with the use of a drug compulsive use and a high tendency to relapse after withdrawal THREE PROCESS required for same effect o TOLERANCE Repeated exposure to the same dose of a drug results in a lesser effect Larger doses Cross Tolerance Development of tolerance to the drug results in decreased sensitivity to another type of drug Barbituates alcohol Cocaine amphetamine MECHANISMS OF TOLERANCE 3 Pharmacokinetic metabolic tolerance o Drug distribution involves adaptations in the pharmacokinetics of a drug All of a drug s effects will develop tolerance because overall decrease in concentration of drug o Metabolic tolerance most common example Involves liver synthesizing more drug metabolizing enzymes then normal when exposed to drug for some length of time Remember tolerance develops because the brain is trying to maintain homeostasis so it will employ mechanisms to counteract the effect of the drug Pharmacodynamic physiological tolerance o Involves adaptations in way individual neurons respond to drug o Drug may induce change in homeostasis brain s attempt to maintain level of functioning within normal limits o Tolerance to drugs that mimic or amplify actions of neurotransmitter tends to decrease receptor activity Decreases receptor activity 2 ways Down Regulation o Decrease in number of functional receptors Desensitization o Decrease in receptors ability to elicit changes no change in receptor number IF o Drug is an agonist Down regulation of receptor Decreased sensitization of receptor o Tolerance to drugs that act as antagonists or dampen actions of neurotransmitter tends to increase receptor activity Increases receptor activity 2 ways Up regulation Sensitization o Increase in number of functional receptors o Increase in receptors ability to elicit changes no change in receptor number IF Drug is antagonist o Upregulation of receptor o Increased sensitization of receptor Context specific behavioral tolerance o Tolerance caused by learned adaptation to drug May learn to adapt to altered state or NS and compensate for impairment When drug is taken in one environment and displays tolerance but loses tolerance when taken in another environment o Examples Animal studies heroin addict returning from jail Potential Mechanism of Tolerance less effects A drug may induce depletion of a NT so that additional administration of drug produces Example Nicotine unbinds slowly saturates the receptor receptors desensitize o Higher doses of nicotine may actually act as antagonist o DEPENDENCE Drug use that results in uncontrollable moods that lead user to use drugs compulsively despite obvious adverse effects Difference from drug abuse use of drugs in doses or ways that result in adverse consequences Two types Psychological dependence Compulsion desire to experience effects of drug because it produces pleasure reduces discomfort o Influenced by context result of learning and memory comes about due to o All abuse prone drugs enhance brain reward OR lower threshold for reward related rewarding effects of drug to fears about withdrawal Physical dependence Occurrence of a withdrawal symptom o Withdrawal symptom set of defined symptoms associated with decrease in blood levels of particular drug Usually effects are opposite from the effects of the drug Withdrawal syndrome varies from drug to drug Withdrawal syndrome due to changes in NS that are responses to chronic presence of drug o When drug is removed compensatory mechanisms are exposed and imbalance results o Duration and intensity of WITHDRAWAL is highly correlated with duration and intensity of DRUG S DIRECT EFFECTS Example Chronic use of drug with short plasma half life induce intense but short lasting withdrawal syndrome Chronic use of drug with long plasma half life weak abstinence syndrome that dissipates slowly o Tolerance precedes dependence For withdrawal symptoms to occur body must have developed tolerance to effect because tolerance involves body producing compensatory mechanisms to counteract drug effects If drug is no longer in system then these mechanisms are still present o REINFORCEMENT something that strengthens behavior pleasurable rewarding or escape from pain discomfort Animals will press levers to receive heroin or cocaine injections Reinforcing properties drug is acting as positive reinforcer Drugs with these properties produce psychological dependence in humans Led to model of addiction o Positive Reinforcement Model of Addiction 1950s animals learned to self administer drugs can learn relationship between drug consumption and relief of withdrawal symptoms Is physical dependence necessary for drug self administration Charles Schuster animals NOT physically dependent would give very small doses of morphine no major physical dependence Pickens and Thompson Demonstrated that cocaine acts are positive reinforcer frequency of lever pressing increases when followed by cocaine vise versa Why does drug continue to act as positive reinforcer when it produces unpleasant negative Positive Reinforcement Paradox consequences Brain Reward Circuits reward thresholds o Olds and Milner found limbic system involved with motivation o Electrical self stimulation increases dopamine levels in nucleus accumbens o Most abuse prone drugs found to enhance brain stimulation reward or lower brain Most found to enhance basal neuronal firing or basal NT release Many drugs alter transmission within dopamine system from VTA projecting to nucleus accumbens o Motivation Control System o Five MAJOR BRAIN REGIONS RF and reward VTA ventral tegmental area Source of dopamine cell bodies sending axon projections to the nucleus accumbens Nucleus accumbens Receives dopamine inputs axon terminals from VTA ALL addictive drugs produce increase of dopamine Increases motor output to produce overall increase in behavior Tells nucleus accumbens where we are and what is happening our Basal Ganglia Hippocampus context Prefrontal Cortex Provides nucleus accumbens with several options for behavior o Primarily dopamine and enkephalin secondarily norepinephrine and GABA Difference between drugs and other natural positive reinforcers o Satiation mechanism o Immediacy and strength of drug s effect o Not everyone becomes addicted Genetic factors Ex children of alcoholics more likely to become one Possible in born difference in NT systems Sociological factors nicotine Family