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Lecture 9

Lecture 9 - Addiction

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Emis Akbari

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PSY398H5S – Motivational Systems Lecture 9 – March 21, 2013 Addiction Motivational States Can Be Regulated By Factors Other Than Tissue Needs •We have so far concentrated on simple forms of motivational states •Human behavior depends on many factors not related to tissue deficit •However, sexual responses and sexual curiosity does not appear to be controlled by deficits of specific substances in the body – nor does aggression •Learned habits and subjective feelings of pleasure can override introceptive feedback signals •i.e. people would rather go hungry that eat something that they have learned to avoid •$10 ---food ? or cigarettes? Pleasure •Pleasure is unquestionably a key factor in controlling motivated behaviors •Sometimes people subject themselves to deprivation to heighten the pleasure obtained when the deprivation is relieved •Since pleasure is subjective, difficult to study experimentally in animals James Olds & Peter Milner, 1954 •One of the most important discoveries for understanding motivation was done in 1954 •Intracranial electrical stimulation of the hypothalamus and associated structures can act as a reinforcer of, or reward for, behavior •Stimulation acts in many respects like ordinary rewards BUT ordinary rewards are only effective if the animal is in a particular drive state (i.e. hunger) • electrical stimulation works regardless of drive state • led to the discovery that there is a neural systems that sub-serve reward •Electrical stimulation of the medial forebrain bundle •Lever pressed 6000 times per hour •Medial forebrain bundle consists of a population of myelinated fibres that project to the VTA •VTA neurons are mostly dopaminergic and project to the NAc •This is the mesolimbic dopamine system Mesolimbic Dopamine System •Study done in 1988 showed that administration of a range of abused drugs (Amph, cocaine, nicotine and opiates) results in an increase in DA release in the NAc •This is also true of natural awards Effects Of Dopamine - Studies • In humans, drugs that reduce dopamine activity (such as antipsychotics) have been shown to reduce both motivation and cause inability to experience pleasure. Maternal behavior (Li et al., 2003) • One study by Pfaus J, Phillips A (1991) found that both anticipatory and consummatory measures of sexual behavior in male rats were disrupted by DA receptor antagonists. Drugs, Molecules & Behavior Neuropsychopharmacology: how drugs affect the nervous system Drug: 2 common meanings: 1) a medicine used in the treatment of disease 2) a psychoactive agent – often additive , drugs of abuse * both however are a substance that, taken in small amounts, has clear effects on experience, mood, emotion , activity & health PSY398H5S – Motivational Systems Lecture 9 – March 21, 2013 Drugs •Some drugs interact with molecules on the membrane •Alter the activity of particular enzymes •Most are ligands and interact with specific receptor molecules •Drugs spread widely in the body, when it comes into contact with a specific receptor it binds and begins a chain of events •Activates or blocks it Drugs – Specificity & Affinity Binding Affinity: The degree of chemical attraction between a ligand & a receptor Efficacy (intrinsic activity): the propensity of a ligand to activate the receptor •LOW AFFINITY: a low affinity drug will quickly uncouple from a receptor- therefore a higher concentration of the drug is needed •HIGH AFFINITY: a high affinity drug will stay together longer and therefore a lower concentration is needed •BOTH: if equal concentrations of both drugs are present the high-affinity drug will bind to more receptors at any given time – therefore will have a more potent affect Dose - Response 50% •Larger doses = higher in circulation •More in circulation = more potent •Increased receptor binding •Dose-Response Curve (DRC): the relationship between drug dose & observed effects •At very low doses, too little is available to provoke a response •At very high doses, receptors are all bound, more will have no effect – receptors are saturated •Effective Dose (ED) 50: the dose at which a 50% response is produced Therapeutic Index •Therapeutic index is the separation between the ED of the drug and toxic doses •This is called Lethal Dose (LD): a dose were 50% of the animals treated die •In this example, this drug has a wide therapeutic index: it’s ED and LD values are far apart and therefore the drug is considered relatively safe •Therapeutic index is the separation between the ED of the drug and toxic doses •This is called Lethal Dose (LD): a dose were 50% of the animals treated die •In this example, this drug has a wide therapeutic index: it’s ED and LD values are far apart and therefore the drug is considered relatively safe Tolerance & Sensitization Tolerance: successive treatments with a particular drug have decreasing effects Can develop in different ways: 1) metabolic tolerance: body’s metabolic organs become effective at eliminating the drug before it has a chance to affect the brain 2) functional tolerance: the target cell may show altered sensitivity down-regulation may occur •Tolerance is a major cause of withdrawal: unpleasant sensations associated with cessation of a drug – during the time that the neural system re-regulates itself •Some drug effects become stronger with repeated treatment = sensitization This contributes to drug craving Dopamine  Dopamine is a “reward” neurotransmitter, and can be triggered by pleasurable activities PSY398H5S – Motivational Systems Lecture 9 – March 21, 2013 like eating, sex, maternal behavior etc.  Can also be triggered by drugs such as alcohol, marijuana and cocaine  Dopamine interacts with the DA receptors and give you the sense of pleasure  However the pleasure sensation lasts only a few seconds  Dopamine is captured by DAT and taken back to the pre-synaptic terminal • Dopamine (3,4 dihyroxyphenylthylamine) is a catecholamine class of monoamines. • It is produced in diverse areas of the brain which are classified into several groups or pathways. The main two of these pathways are:- – Mesostriatal pathway: substantia nigra to striatum  – Mesolimbocorticalpathway: midbrain through limbic system into the cortex. Roles Of Dopamine Dopamine as a neurotransmitter • Mesostriatal pathway: motor control, loss of neurons result in Parkinson’s disease • Mesolimbocortical pathway: verbal learning (amygdala), reward and reinforcement, excess activity causes Schizophrenia. Dopamine as a hormone • released by the hypothalamus • inhibit the release of prolactin from the anterior lobe of the pituitary. Drugs & Dopamine Receptors • Dopamine Agonist. These drugs bind to dopamine r
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