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Lecture 4

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Suzanne Erb

Lecture 4 – The Neurobiology of Reward Addiction • Dependence • Tolerance • Sensitization • -These three don't always occurred during addiction and can occur in the absence of addiction • Drugs of abuse- have rewarding effects which cause individuals to enjoy taking the drug WHAT IS REWARD?? - A reward can be something pleasurable, can take away unpleasant things, can have positive emotional valence, and can serve as an incentive in the context of learning (eg: reinforcing) (positive or negative reinforcement) -Something neutral that can produce reward is called classical or pavlov conditioning -Individuals seek rewards and stimuli from the environment Different types of rewards •Natural rewards •e.g., food, water, sex, nurturing - Cause pleasure when procuring the rewards - naturally adaptive roles •Artificial rewards •e.g., drugs, money (gambling) - Act on the same brain systems that natural reward systems work on Olds and Milner (1954) • discovered that electrical stimulation of certain areas of the brain was rewarding and reinforcing -They put a rat in a Skinner box with an electrode in the brain -In the Skinner box was a lever that the rat could press to allow the region of the brain with the electrode to be stimulated. -They identified what brain regions are capable of maintaining brain stimulation of reward by looking at the region that the rat self-stimulated by pressing the lever -They found these regions capable of causing rats to self-stimulate Brain stimulation reward sites include: brain stimulation reward sites include: •Medial Forebrain Bundle (MFB) •Ventral Tegmental Area (VTA) •Nucleus Accumbens •Frontal Cortex •Lateral Hypothalamus •Substantia Nigra •Striatum, Amygdala, Hippocampus, Thalamus, Cerebellum •Locus Coeruleus - Primary Reward Pathway: consists of MFB, VTA, Nucleus Accumbens and Frontal Cortex - In particular the VTA and dopaminergic projections which is the primary reward pathway. The MFB's and nucleus accumbens and prefrontal cortex are also part of the primary reward pathway. • The DA hypothesis of reward has instigated a considerable amount of research over the last few decades. • However, much of that research can lead one to conclude that it is oversimplified to consider DA as the sole mediator of primary “reward”, or primary motivation for natural stimuli such as food, water, and sex. -Related behaviour to dopamine because the main projection region is dopamine and when stimulating, there is more dopamine activity in the brain. -Dopamine blockers stop rat from brain stimulating -Graph – microdialysis cerebrospinal fluid to test drug levels (100% = baseline) • Imaging studies are often used to support the idea that nucleus accumbens mediates pleasure. -Dopamine transmission especially in the nucleus accumbens of the primary pathway mediates all positive reinforcing stimuli. Drugs of abuse hijack this pathway and cause it to react to both artificial and natural drugs differently. -Drugs increase dopamine in nucleus accumbens -Oversimplified to consider it dopamine (DA) as the sole mediator of the primary reward  there is more factors affecting this and humans use dopamine for more than just pleasure -Nucleus accumbens also reacts to the adverse situations such as stress, aversion, hyper arousal/irritability • But imaging research also demonstrates that the nucleus accumbens responds to: • stress • aversion • hyperarousal/irritability • Thus, concepts about role of DA in drug-induced euphoria, dependence, and addiction have undergone revision. -Benzodiazepam – blocking dopamine can take away aversive effects Addiction •Dependence •Tolerance •Sensitization Addiction: • A related set of terms describes behavioral patterns of excessive or chronic drug taking that can result in deleterious effects. -Consider the idea that drug addiction leads to aversive and compulsive behavior that one cannot control • These terms include: – Drug abuse : doesn't not mean substance dependence – drugs having negative affect – Drug dependence : need for drug – when terminated, there is a withdrawal symptom – Drug addiction: psychological need to take drug -If physiological need is not related to psychological need for the drug (both, one or the other) Dependence • A state in which an organism functions normally only in the presence of the drug - Desire or craving • there are two types of drug dependence: A. physiological or physical dependence B. psychological or motivational dependence • Some psychotropic drugs have a strong potential for producing both physical and psychological dependence. - Psychotropic drugs – E.g. sedative hypnotics eg. barbiturates, opiates, and alcohol -Some with minimal potential for physical dependence and absence of psychological dependence eg: nasal sprays and opiates • Others appear capable of inducing one without the other. - Other drugs produce psychological dependence but no physical dependence (e.g. reduce ability to feel pleasure) • Still others do not induce either to any significant degree. A. physiological or physical dependence • characterized by various physical disturbances or withdrawal symptoms when the drug is removed •withdrawal symptoms are generally the opposite of the direct effect of the drug Bold = physical symptoms Grey =psychological effects Withdrawal symptoms are opposite effects of drugs symptoms • Duration and intensity of an abstinence syndrome correlate with duration and intensity of a drug’s direct effects. • Abstinence symptoms are not typically displayed unless the individual has consumed the drug for several days or weeks at high dosage levels. • With sufficiently high dosages, signs of abstinence may occur in a short span of time—following high drug concentrations for 12 hours or so. • Once physical dependence exists and the person becomes familiar with the symptoms of abstinence, the person may develop a craving for the drug based on the person’s fear or anxiety of experiencing the abstinence syndrome. Figure in text about dependence -Direct drug effect plus withdrawal affect -Arrows= where drug is given -System is able to recover quickly so no withdrawal -Now if the drug is given at higher and more frequent intervals and the body cannot recover then there will be a withdrawal effect -With longer acting drug you get longer withdrawal symptoms -high drug concentration for a short period of time cause withdrawals B. Psychological or motivational dependence • cha
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