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Emotions
- Common emotions– happiness, anger, surprise, fear, sadness
- Very subjective– same stimulus does not give same response in all people in all situations
- Emotions are strongly tied to the visceral motor system (emotional feeling)
- Also tied to somatic muscle responses– especially facial muscles (emotional expression)
- Limbic system– brain areas especially important for emotions (emotional thinking)
- Affective (mood) disorders– e.g. depression
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Abraham Lincoln:
I am now the most miserable man living. If what I feel were equally distributed to the whole human family, there would not be one cheerful face on earth. Whether I shall ever be better, I cannot tell; I awfully forebode I shall not. To remain as I am is impossible. I must die or be better, it appears to me.
Lincoln was unconscious following a horse kicking him in the head for 24hrs at 9 yrs old.
He was clubbed on the head during a robbery attempt in 1828.
https://en.wikipedia.org/wiki/Medical_and_mental_health_of_Abraham_Lincoln
http://www.theatlantic.com/magazine/archive/2005/10/lincolns-great-depression/304247/
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Lincoln's melancholy
Abraham Lincoln:
I am now the most miserable man living. If what I feel were equally distributed to the whole human family, there would not be one cheerful face on earth. Whether I shall ever be better, I cannot tell; I awfully forebode I shall not. To remain as I am is impossible. I must die or be better, it appears to me.
Visceral (autonomic) motor system
- Two main subdivisions– sympathetic and parasympathetic subsystems
- Sympathetic mobilizes the body’s resources for dealing with challenges. Fight or flight response
- Parasympathetic deals with energy storage. Calms the body
- Major locus of control is the hypothalamus and brainstem areas
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- Visceral
- relating to deep inward feelings rather than intellect
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Autonomic motor system
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Sympathetic Fight or flight, preganglionc: in the intermediolateral column. Postganglionic: Sympathetic chain
blood vessels in skin and gut contract, rerouting blood to muscles
hairs stand on end, piloerection making us look more fearsome, bronchi dilate for incr oxygenation, heart rate accelerates. Sympathetic activity also stimulates adrenal medulla to relesase adrenaline and noradrenaline into the bloodstream to mobilize glucagon release from pancreas.
Parasympathetic:
Preganglionic is in the brainstem or sacral spinal cord, Peripheral ganglia in close to the organ they control (think ciliary ganglion or cardiac plexus)
sympathetic:
preganglionic is in spinal cord, peripheral ganglia is in the specialized sympathetic chain ganglia
Facial expression of emotion
- Duchenne de Boulogne
- Facial muscle stimulation can create a variety of expressions recognizable as emotion
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Emotions can trigger facial muscles that can’t be done on purpose.
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Expression of emotion
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animals express emotion as well—
Facial expression of emotion
Two pathways to get to facial muscles that display emotion– voluntary and emotional pathways are separable.
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extrapyramidal system: is a neural network that is part of the motor system causing involuntary movements
pyramidal pathways (corticospinal and some corticobulbar tracts) may directly innervate motor neurons of the spinal cord or brainstem
extrapyramidal system centers on the modulation and regulation (indirect control)
Extrapyramidal tracts are chiefly found in the reticular formation of the pons and medulla, and target neurons in the spinal cord involved in reflexes, locomotion, complex movements, and postural control
paresis: muscle weakness
Hypothalamus as a coordinator of emotional behavior
- Hypothalamus as a critical center for coordination of both the autonomic and somatic components of emotional behavior
- Lesion huge areas of the forebrain in cats and angry behavior occurs spontaneously, including the autonomic correlates of anger. Increased blood pressure and heart rate, dilation of pupil, hair raising. Also contained somatic motor components such as arching the back and tail. Called sham rage
- Sham rage found to require the hypothalamus
- Stimulation of discreet parts of hypothalamus could elicit different behaviors associated with anger
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Hypothalamus as a coordinator of emotional behavior
- Phillip Bard / Walter Hess, early 1900s. Conducted seminal studies that determined the hypothalamus is a critical center for coordination of both the autonomic and somatic components of emotional behavior
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started by removing cerebral hemispheres of cats, when anesthesia wears off they acted as if enraged. Involved all the autonomic components of the sympathetic nervous system. Called sham rage because no obvious target.
Sham rage: Angry behavior occurred spontaneously included autonomic correlates of anger. Increased blood pressure and heart rate, dilation of pupil, hair raising. Also contained somatic motor components such as arching the back and tail.
Connection from ventral hypothalamus to midbrain needs to be present to elicit sham rage.
Bard suggested that emotional behaviors are often directed towards self-preservation (point also made by Charles Darwin).
Affective attack expression
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General connectivity of emotions
- Both a volitional (with deliberate action) and a non-volitional component. Are in separate pathways. Both pathways ultimately lead to motor neuron pools that activate muscle contraction or smooth muscle/gland secretions
- Lateral projections control specific movements or emotional behaviors, medial projections provide support for these behaviors
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Descending systems that control somatic and visceral motor pathways in the expression of emotion
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- major targets of the hypothalamus is the reticular formation (tangled nerve web of over 100 cell groups including those that regulate sleep/wakefulness, cardiovascular function, respiration, urination, vomiting, swallowing). Reticular output is to somatic and visceral motor effector systems.
How does your brain regulate emotions?
- Anatomists had shown that there was a subregion of the brain that formed a rim around the corpus callosum and the medial aspects of the cerebral hemispheres
- Contains the hippocampus and cingulate gyrus
- These areas found to form a circuit with other areas, including hypothalamus–amygdala, and parts of the thalamus. Together these areas make up the limbic system
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Limbic system
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The limbic system.
Green is modern view of limbic system critical for processing emotion. Blue includes other areas of the traditional limbic system such as the hippocampus and mammillary bodies that are not considered critical to circuits for emotional processing.
orbitofrontal and medial prefrontal cortex together with the amygdala are especially important components of the limbic systm.
- mammilary bodies are part of the posterior hypothalamus and is important for interconnecting the cingulate cortex with the hypothalamus through the anterior nucleus of the thalamus
- hippocampus projects back to the hypothalamus via the fornix
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Limbic system
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Limbic system
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amgydala—> ventral basal ganglia —> mediodorsal nucleus of thalamus —> orbital and medial prefrontal cortex —> amygdala
amgydala, Latin for ‘almond’
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Amygdala
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amgydala is in the anteior-medial part of the temporal lobe. Rostral to hippocampus
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three major functional and anatomical subdivisions
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medial group
- connections with olfactory bulb and olfactory cortex
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basal-lateral group
- large in humans
- major connections to orbital and medial prefrontal cortex of frontal lobe and association cortex of anterior temporal lobe
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central and anterior group
- connections to hypothalamus and brainstem (visceral sensory structures like nucleus of solitary tract and parabrachial nucleus)
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hypothalamus receives unprocessed sensory inputs, amygdala receives processed sensory inputs (cortex and thalamus)
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highly complex stimuli often needed to evoke response in amygdala (e.g. facelike neurons)
Crude lesion studies
- John Downer (London in 1950’s) removed the temporal lobes of monkeys and witnessed weird emotional behaviors
- Unable to recognize objects, although not blind (why?)
- Bizarre oral behaviors
- Hyperactivity and hypersexuality, making physical contact with virtually anything
- No longer showed fear. Neither to humans or to snakes
- Eventually the fear behaviors was narrowed down to a region called the amygdala through selective lesion studies
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Patients with amygdala damage exhibit diminished emotional fear recognition and expression
Patient S.M. can’t recognize the emotion of fear in photographs. She also exhibits little fear herself (e.g. to dangerous animals, scary houses, films, etc)
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patient SM has rare autosomal recessive condition called Urbach-Wiethe disease. Disorder of bilateral calcification an atrophy of anterior-medial temporal lobes. Both amygdalas are extensively damaged. Little to no injury of the hippocampus.
She has no motor or sensory or intelligence or memory or language impairment. However she can’t recognize the emotion of fear in photographs. Furthermore, she exhibits little fear herself (to dangerous animals, scary houses, films, etc).
Patients with amygdala damage exhibit diminished emotional fear recognition and expression
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Adolphs et al., 1995. Subject with bilateral amygdala lesions was asked to draw facial expressions of emotions.
Fear conditioning
- Pair a normally neutral stimulus with an inherently aversive one. Over time the animal will show behaviors to the neutral stimulus similar to that when given the aversive one. The animal learns to attach new meaning to a stimulus through classical conditioning
- Can use this assay to determine what areas of the brain are required for the learned behavior
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Classic experiments demonstrating fear conditioning in an infant
A white rat presented to an infant does not innately elicit fear, but pairing the rat with an aversive noise, produces crying and attempts to crawl away, even when the rat was presented without the noise.
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Classic experiments from Watson and Rayner demonstrating fear conditioning in an infant
As early as the 1920s, fear conditioning was demonstrated in infants. A white rat presented to an infant does not innately elicit fear, but pairing the rat with an aversive noise, produces crying and attempts to crawl away, even when the rat was presented without the noise.
Fear conditioning in rats
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notice incr blood pressure, visceral response after the association is made and how it is maintained
Pathways involved in fear conditioning
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CE – central nucleus, LA lateral Nucleus
CG– central gray or PAG (periaqueductal gray). Primary control center for descending pain modulation. Enkephalin releasing neurons that project to raphe nuclei (and 5-HT in turn excites inhibitory interneurons in the spinal cord dorsal horn). Role in analgesia and defensive behavior. Responsible for the ‘freezing’ behavior of conditioned fear, the arresting of somatomotor activity.
LH– lateral hypothalamus. Contains orexinergic neurons. Projects widely throughout nervous system. Promotes feeding behavior, arousal, reduces pain perception, regulates body temperature, digestive functions and blood pressure. Glutamate, endocannabinoids (anandamide), and orexin neuropeptides are main neurotransmitters in orexin neurons. Robust projections to posterior hypothalamus, tuberomammillary nucleus (histamine projection nucleus in posterior hypothalamus. Sole source of histamine pathways in human), arcuate nucleus (neuroendocrine neurons in mediobasal hypothalamus, prolactin, GHRH, ghrelin, neuropeptide-Y), paraventricular hypothalamic nucleus.
PVN– paraventricular nucleus of hypothalamus. Contains groups of neurons activated by stressful or other physiological changes. Release oxytocin or vasopressin into circulation through terminals in the pituitary.
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Important properties of LTP
- Spatial localization (synaptic input specificity)
- Associativity (between synapses within the post-synaptic neuron)
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- Properties consistent with role as specific coincidence detector
- Not generalized across whole neuronal ensembles, but localized
- Associativity utilized for associative learning or classical/Pavlovian conditioning (great early 20c russian physiologist, Pavlov's dogs (dinner bell association with food presentation and salivation))
at Schaffer collateral axon synapse betwen CA3 and CA1
- NMDA receptor opening leads to strengthening of synapses
- weak stimulation at pathway 2 can lead to synapse strengthening/potentiation through associative mechanisms-- EPSP summation
Model for associative learning in the amygdala
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The amygdala as a key node in the brain network for emotional processing
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- orbito and medial prefrontal cortex
- prefrontal cortical regions in the frontal lobe associate information from every sensory modality
- amygdala projects to mediodorsal nucleus of thalamus-- this in turn projects to the prefrontal association areas
- innervates nueons in ventral basal ganglia that receive major corticostriatal projections
Amgydala and connections to prefrontal cortex and basal ganglia regulates selction and initiation of behaviors need to obtain rewards (and avoid punishments)
Feelings may be a kind of emotional working memory. Containing both immediate conscious experience of implicit emotions and explicit processing of semantic thought, orbito and medial sectors likely areas for these assocaition be maintained in conscious awareness
Model for the awareness of emotional feelings
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Emotions are lateralized
- Right hemisphere is especially important for the expression and comprehension of the affective aspects of speech (emotional sides of language)
- People with lesions on the right side equivalent of Broca’s area speak in monotones. Unable to change tone to relay things like anger
- Mood. Left side more associated with positive emotions and the right side more associated with negative emotions
- Depression often associated with left side damage, right side damage leads to undue optimism
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smile asymmetries in facial expressions, most individuals more quickly and fully express emotions with left facial musculature than the right
Mood disorders– depression
- Can be unipolar or bipolar
- Unipolar depression affects 5% of world’s population. 8 million Americans at any given time
- Average age of onset 28 years. More common in women than men
- Bipolar disorders– have a manic phase. 1% of people have it at some point during lifetime. Affects men and women equally
- Account for a large fraction of suicides
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Treatments for depression
- Monoamine oxidase inhibitors that increase monoamine concentration at synaptic terminals– e.g. Iproniazid
- Monoamine transporter inhibitors– e.g. Imiprmine and fluoxetine (Prozac). Fluoxetine selectively inhibits serotonin reuptake as a selective serotonin reuptake inhibitor
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Anxiety disorders
- Most common types of psychiatric disorders, include anxiety, phobias, panic disorders, obsessive-compulsive disorder
- Often associated with fatigue, muscle tension, and sleep disturbance. 5% of people report some type of general anxiety disorder
- Barbiturates– reduce anxiety but also are potent sedatives. Overdose is lethal
- Benzodiazepines– reduce anxiety without as much sedation. Harder to overdose on benzodiazepines
- Both drugs bind to the ionotropic GABA receptors and enhance GABA transmission
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Benzodiazepine mechanism of action
- Benzodiazepines increase the affinity of the receptor for GABA
- Barbituates can activate the GABA receptor independent of GABA
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Act at the level at the interface of the alpha and gamma subunits. Different neurons express different gamma subunits. Six different genes for the alpha subunit. Benzodiazepines only can interact with the a1,a2, and a5 subunits, have a conserved histidine.
Drug abuse and addiction
- Emotional processing in the limbic system signals the presence or prospect for reward and punishment, and activates programs to procure rewards and avoid punishment
- Most known drugs of abuse (heroin, cocaine, ethanol, opiates, marijuana, nicotine, amphetamines) act on the limbic circuits
- Most act by altering dopamine circuits that go through the ventral basal ganglia
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all act by changing the neuromodulatory influence of dopamine for processing reinforement signals in nucleus accumbens, leading to the strenghthening of circuits underlying addictive behavior in limbic systems
Functional and anatomical organization of the limbic loop through the basal ganglia
- Nucleus accumbens– contains MSNs
- Ventral tegmental area (VTA)– provides dopaminergic input to the to nucleus accumbens
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Recall the non-motor loops we discussed in our study of the basal ganglia.
Much like the direct pathway. Inputs from different parts of cortex, including amygdala.
to MSNs in ventral striatum the nucleus accumbens. These gabaergic projections then inhibit inhibitory projections in the in the ventral globus pallidus called the ventral pallidum. So there is a disinhibitory effect, much as we discussed before for other basal ganglia loops.
nucleus accumbens and VTA are the main sites wher drugs of abuse interact with signals for emotional reward
serotonin pathways
- mood
- memory processing
- sleep
- cognition
dopamine pathways
- reward (motivation)
- pleasure, euphoria
- motor function (fine tuning)
- compulsion
- perserverance
- decision making
Changes in the activity of dopamine neurons in the VTA during stimulus–reward learning
Recordings from VTA dopamine neurons in awake monkey. VTA signals the presence of an expected reward
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The VTA signals the occurrence of a reward relative to its prediction
- Schultz Neuron 1997
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Stimulation of reward pathway is incredibly powerful
- Self stimulation experiments have demonstrated that rats will bar press for stimulation of the VTA or NAc
- Olds and Milner, 1954, J Comp Physiol Psychol, 47
- This behavior can be blocked by cutting the pathway from the VTA or by administering dopamine antagonists
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Drugs of abuse affect dopamine projections from the VTA to the nucleus accumbens
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Exposure to drugs of abuse causes long-lasting enhancement of excitatory input to VTA dopamine neurons, increasing AMPA/NMDA receptor ratio at these synapses.
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Circuits involved in drugs of abuse
- Nicotine enhances input onto VTA by presynaptic excitation
- Opioids, benzodiazepines, and cannabinoids act by hyperpolarizing GABAergic neurons
- Ethanol boosts dopamine concentrations– mechanism unknown
- Cocaine blocks dopamine reuptake via the plasma membrane dopamine transporter (DAT)
- Ecstasy causes dopamine release in vesicle independent manner, inhibits
- Dopamine degradation and increases dopamine biosynthesis
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Specifically, studies in primates and rodents have shown that many VTA dopamine neurons encode reward prediction errors. This error signal is hypothesized to direct synaptic plasticity in target neurons in the nucleus accumbens and prefrontal cortex for reinforcement-based learning. If VTA dopamine neurons signal a reward, the action or behavior that immediately preceded the reward is reinforced through dopamine modulation of downstream circuits (see Figure 10–44). Drugs of abuse bypass natural signals that activate these dopamine neurons, thus dissociating the reward system from its natural stimuli. Specifically, by increasing dopamine concentration at dopamine neurons’ presynaptic terminals, drug consumption mimics dopamine neuron activation; this reinforces the preceding actions, include drug consumption itself. Thus, addictive drugs hijack the brain’s reward system and exploit mechanisms that otherwise regulate learning and motivational
long-term changes addicts:
- Decreases in CREB transcription factor in NAc (and extended amygdala)
- Decreases in metabolism in orbito frontal cortex (OFC)
- Decreases in dopamine D2 receptor binding
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Drugs of abuse act on endogenous neurotransmitter receptors and transporters
| Drug | Endogenous ligands | Mechanism of action |
|---|---|---|
| Nicotine | acetylcholine | Agonist of ligand gated channels (nAChR) |
| THC | anandamide, 2AG | Agonist of cannabinoid receptors (GPCRs) |
| Opioids | enkephalin, ß-endorphin, Dynorphin | Agonist of opioid GPCRs (µ,∂,k) |
| Cocaine | Inhibits 5-HT transporters, DAT, NET. Increased DA, NA, 5-HT in synaptic cleft. | |
| Amphetamine | Inhibits MAO, NET, and VMAT. Increased DA and NA in synaptic cleft. | |
| MDMA (ecstasy) | Inhibits 5-HT transporters and VMAT. Increased DA, 5-HT, NA in synaptic cleft. |
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Cocaine
DAT: dopamine transporter, extracellular
NET: NA transporter, extracellular
MAO: monoamine oxidase, intracellular.
- : Catalyzes oxidation of monoamines (serotonin, melatonin, norepinephrine, epinephrine (MAO-A) and dopamine, tyramine, tryptamine (MAO-A & MAO-B)
- : bound to outer membrane of mitochondria of most cell types in the body.
- VMAT2: vesicular monoamine transporter, intracellular
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blocking VMAT2 can cause reverse transport direction (cytosol to synaptic cleft) for monoamine transporters. Particularly for MDMA and amphetamines
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SLC18A2 gene
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transports monoamines—particularly neurotransmitters such as dopamine, norepinephrine, serotonin, and histamine from cytosol into synaptic vesicles
-MDMA enters monoamine neurons by acting as a monoamine transporter substrate (i.e., a substrate for DAT, NET, and SERT)
Addictive drugs hijack the brain’s reward system by enhancing the action of VTA dopamine neurons
- Drug addiction: compulsive drug use despite long-term negative consequences
- All drugs of abuse increase dopamine concentration at the output targets of the ventral tegmental area
- Nucleus accumbens– processes reward information
- Prefrontal cortex– goal selection and decision making
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23 percent of individuals who use heroin become dependent on it. Altered conscious regulation of your behavior. 1 in 5.
http://www.samhsa.gov/
number of dependent users a year after first use 2008:
- hallucinogens and sedatives 2%
- pain relievers and alcohol 3%
- heroin 13%
- crack cocaine 9%
- marijuana 6%
- stimulants 5%
- powder cocaine 4%
Key components of limbic system reward circuits
- VTA–nucleus accumbens pathway:
- Dopamine pathway
- Acts as a rheostat of reward. Tells other brain centers how rewarding an activity is. The more rewarding an activity is deemed, the more likely the organism is to remember it well and repeat it
- Neurons from ventral tegmental area (VTA) to nucleus accumbens (major neurotransmitter is dopamine)
- Critical pathway for drug addiction
- Amygdala:
- Helps assess whether an experience is pleasurable or aversive and whether it should be repeated or avoided to forge connections between an experience and other cues
- Hippocampus:
- Recording the memories of an experience
- Frontal cortical regions:
- Coordinates and processes all this information and determines ultimate behavior of the individual
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