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University of Toronto Scarborough
Suzanne Erb

PSYC62: Drugs and the Brain Lecture 4: Tolerance, Sensitization, Dependence, and Addiction (Chapter 6) Outline  Neurobiology of reward  Addiction o Dependence o Tolerance o Sensitization Neurobiology of brain reward: WHAT IS REWARD??  Something that produces a pleasurable experience  Would take away a pleasant experience would be rewarding  Positive emotional, pleasurable, makes us feel good, gives us an incentive  Leads to an reward, behaviour will be repeated in the future  The consequence will increase the positive reinforcement  Something neutral will repeated and associated with unconditioning Different types of rewards 1. Natural rewards o e.g., food, water, sex, nurturing o have some sort of evolutionary or adaptive 2. Artificial rewards o e.g., drugs, money (gambling) o Do not play an adaptive role for the organism but can strong control behavior  Both these rewards act on the same brain mechanisms Olds and Milner (1954)  Discovered that electrical stimulation of certain areas of the brain was rewarding and reinforcing o Olds and Milner were scientists at McGill and established the reward mapping in rodents  Brain Stimulation Reward o They learned that there were a whole of regions that the rat learned to press the lever for (reward sites) o Identify what brain region of the rat are capable of maintaining brain stimulation reward -to which of these brain region will the brain involuntarily press the lever Neurobiology of Brain Reward  Brain stimulation reward sites include: o Medial forebrain bundle (MFB) o Ventral tegmental area (VTA) o Nucleus accumbens o Frontal cortex o Lateral hypothalamus o Substantia nigra o Striatum, amygdala, hippocampus, thalamus, cerebellum o Locus coeruleus  Regions that support brain stimulation in the rat  MFB - connects a lot of the other areas in this list - extensive system  MOB, VTA, nucleus acumbens, and frontal cortex are the primary reward pathway – Based on their work, and other groups, all 4 were primary reward pathway  parts of the medial forebrain bundle  if electrode planted in active regions of the PRP, the animals will have robust learning and active stimulation  Electrode outside the region, the rat felt no stimulation Neurobiology of Brain Reward  Olds and Milner found that when electrodes were placed in these areas and especially the nucleus accumbens, the rats kept pressing the levers  Major projector in the circuitry is dopamine Neurobiology of brain reward  The DA hypothesis of reward has instigated a considerable amount of research over the last few decades  Dominant hypothesis of drug addiction - dopamine within the primary reward circuit and particular in the nucleus accumbens mediates all rewards - pharmacological antagonists of dopamine decreased effects was evidence for the hypothesis - all drugs of abuse share the fact that they increase extracellular dopamine neurotransmitters  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  It is not all about the dopamine and other transmitters are also involved Neurobiology of brain reward  Extracellular levels of dopamine is much higher with cocaine rather than saline (control) - dramatic increase in dopamine by cocaine (works with amphetamine, alcohol, etc)  Dopamine levels as baseline  Robust increase in extracellular conc. of dopamine Neurobiology of brain reward  Imaging studies are often used to support the idea that nucleus accumbens mediates pleasure.  But imaging research also demonstrates that the nucleus accumbens responds to: o Stress o Aversion o Hyperarousal/irritability  Thus, concepts about role of DA in drug-induced euphoria, dependence, and addiction have undergone revision.  Too simplistic to label dopamine as the pleasurable transmitters - dopamine activity are also responsive to stressors and aversive stimuli  participates in complex behaviour  A drug reducing anxiety (should increase dopamine right?) - nope it actually decreased dopamine transmission  Drugs that induce anxiety actually increases dopamine levels  Dopamine is still very importantly involved in addiction - we have to move beyond this dopamine synapse view of drugs and pleasure - more dopamine you have in the nucleus accumbens (more complicated than that) Addiction  A related set of terms describes behavioral patterns of excessive or chronic drug taking that can result in deleterious effects  Excessive use of drugs that become involuntary or becomes out of control and that interferes with the individual's functioning and adverse effects  These terms include: o Drug abuse: not synonymous with substance dependence or addiction - someone who abuses do not have to have a drug addiction or drug dependence o Drug dependence and Drug addiction (these terms can be used interchangeably) Dependence  A state in which an organism functions normally only in the presence of drug (the drug is onboard - real or perceived need of the drug for normal psychological functioning)  Dependence is defined with the abstinence syndrome  There are two types of drug dependence: A. Physiological or physical dependence  Immergence of a abstinence syndrome - when the receptors are deprived of the drug, there is a physical adverse effects B. Psychological or motivational dependence  Strong compulsion or craving for the drug in order to experience the pleasurable effects of the drug - positive and negative reinforcement can both be at play here (taking the drug can make them happy or taking the drug can remove a adverse emotion)  Some psychotropic drugs have a strong potential for producing both physical and psychological dependence o Sedatives (alcohol and barbiturates and opiates) can produce psychological and physical dependences o Physical dependence - drugs that produce a strong physical reaction but not because the individuals are seeking or craving the drug - mixed agonist and antagonist - morphine o Psychological dependence - psychostimulants (cocaine or amphetamines)  Others appear capable of inducing one without the other  Still others do not induce either to any significant degree o Don't induce any psychological or dependence - antipsychotic or antidepressants Dependence  A. physiological or physical dependence o Characterized by various physical disturbances or withdrawal symptoms when the drug is removed o Withdrawal symptoms are generally the opposite of the direct effects of the drug o E.g., opiates Opiates  Short-Term Effects: Sedation, Analgesia, Respiratory depression, Constipation o Euphoria  Withdrawal Effects o Restlessness; insomnia, Hyperalgesia, Hyperventilation, Diarrhea, Dysphoria; irritability  Usually opposites effects of the drug with physical dependence  Euphoria is psychological effect, whereas the others are all physical Dependence  Duration and intensity of an abstinence syndrome correlate with duration and intensity of a drug’s direct effects o The longer acting a drug is and the higher the dose, the longer and more intense the abstinence syndrome o Dependence takes time to emerge in most cases  Abstinence symptoms are not typically displayed unless the individual has consumed the drug for several days or weeks at high dosage levels  With suffic
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