Brodmann's Areas

• Primary Somatic Sensory Cortex: 3-1-2
• Primary Motor area: 4
• Premotor and supplementary motor area: 6
• Frontopolar cortex: 10
• Primary Visual Area: 17
• Wernicke's speech comprehension: 22, 39, 40
• Primary Auditory Area: 41
• Broca's Expressive speech area: 44, 45

Unique Features

of

Association Cortices

• inputs: primary and secondary sensory and motor cortices, the thalamus and the brainstem
• Outputs: hippocampus, basal ganglia, cerebellum, the thalamus and other association cortices
• parietal assoc cortex for attending to complex stimuli in the external and internal env
• temporal assoc cortex major role in identifying the nature of such stimuli
• frontal assoc cort critical for planning appropriate behavioral responses to the stimuli

Parietal Association Cortex

• primarily attending to complex stimuli in the external and internal environment
• lesions in this association cortex typically lead to deficits referred to as contralateral neglect syndrome (unable to acknowledge his left side)
• motor, somatic sensation and visual abilities maintain intact by fail to acknowledge left visual and right side of body
• right lesion in parietal cortex (Stroke) more severe than left side because right parietal mediates both sides of body and external space (left lesions therefore compensated for)

Parietal Lesions

• Right hemisphere lesion: sevee left neglect
• Left hemisphere lesion: minimal right neglect(compensation)
• partial bilateral lesion: severe right neglect, knocks out the left hemisphere and the part of right hemisphere that does right field

Temporal Association Cortex

lesions

• lesions cause inability to recognize or identify complex stimuli
• amage to either the left or right hemisphere can result in difficulties of recognizing complex objects or face recognition (agnosia)
• severity and major char of the deficits are largely dependent upon the laterality, location and size
• lesions or right temp result in agnosia for face and object recognition
• lessions of the left temp lead to difficulties with langwuage related material
• recognition deficits more apparent near occipitotemporal gyrus, whereas language usually associated with the lateral surface of temporal cortex

Agnosia

• damage to either the left or right hemisphere (temporal assoc cortex lesion) can result in difficulties of recognizing complex objects and face recognition
• different from the neglect caused by lesions of the parietal asoc cortex
• in contract to neglect, patients with agnosia typically can acknowledge the presence of a stimulus but are unable to report what it is

Frontal Association Cortex

(Lesions)

• have much more diverse and often hardly-defined manifestations
• generally defined as the brain area which is responsible for planning an appropriate response to a stimulus
• largest association cortex in humans
• receives and integrates info from sens, motor, parietal and temporal association cortices
• seem normal in casual conversation 
• people with lesion have disinhibition and of the resulting loss of behavioral control
• also have great deal of difficulty planning and organizing their lives

Wisconsin Card Sorting Task

• assessment of the frontal association cortex
• subject is asked to place an appropriate response card when the examinar introduces a sample card sequence (examiner does not tell sorting rule and wheter examinee is right or not)
• then indicates whether response is right or wrong and after 10 consecutive correct responses, changes the sorting rule by saying wrong
• they must than do 10 more consecutive ones before switching again, rule should be changed 6 times
• patients with frontal lobe lesions do not do well (planning deficits)

Apraxia

• inability to execute a complex motor behavior
• may be produced by a destructive lesion in the parietal association cortex, premotor cortex, or supplementary motor cortex
• effected individuals muscles are fine but he/she is unable to coordinate different muscles to execute complex motor behavior
• apraxia is more severe when the dominant hemisphere is affected

Language comprehension and production

• highly lateralized and predominantly in the dominant (usually left) hemisphere
• although functionally connected to sensory and motor areas, can function independently
• ability to control the muscles of the larynx, pharynx, mouth and tongue can be compromised without significant effect on using language to communicate
• damage to auditory cortex may not affect language functino
• lesion in language related association cortex has profound effect on production and comprehension (aphasia)
• patients with aphasia do not usually exhibit any deficiences in sensory nor motor function
• of 400,000 strokes, 80,00 of them develop aphasia

Temporal-parietal region

(wernicke's area)

• lesions involving the posterior part of the superior temporal gyrus and adjoining parts of the inferior parietal lobule (angular and supramarginal gyri, brodmann's areas 22, 39 and 40) produce receptive aphasia
• patients with wernicke aphasia are not aware of their disability and therefore are much less frustrated and depressed than patients with Broca's aphasia

Receptive Aphasia

• can be sensory or fluent aphasia
• from lesion in wernicke's area
• patients are unable to understand spoken, written, or visually relevent language
• classic example of multimodal association cortex
• may speak but their speech doesnt make sense
• unaware of their disability

Frontal Lobe Lesion

(Broca's Area)

• lesions in posterior part of the inferior frontal gyrus(pars opercularis and pars triangularis, 44 and 45) produce motor or nonfluent aphasia
• patient can understand speech but is unable to express their ideas in spoken (or written) words
• patients having broca's aphasia have difficulty saying anything
• often pause to search for the right word

Conduction Aphasia

• interruption of the arcuate fasciculus connecting wernickes and brocas areas
• patient has poor repetition of a sentece spoken by the examiner but maintains relatively good comprehension (and production) of speech

Non-dominant hemisphere in language

• non-dominant is usually right hemisphere
• contributes to language productino and comprehension
• important for communicative and emotional prosody (stress, timing, and intonation)
• patients with brocas lesion in non-dom may produce inappropriate intonation in their speech
• lesion in the wernicke's area may result in difficulties understanding emotional aspects of speech (dont understand jokes)

Cerebral Dominance

• ability of one cerebral hemisphere to predominately control a specific task
• trauma of left hemisphere would likely affect speech, reading and writing whereas right hemisphere would likely affect judgment of distance and determining direction
• dominant hemisphere (usually left): 90% of right hand people and 60% of left handed. responsible for language, speech and calculation (rational side)
• nondominant hemisphere (usually right): responsible for 3D or spatial perception and nonverbal ideation(artistic side) nondominant hemisphere is also very advanced in face recognition

Wada Test

• determines dominant hemisphere
• sodium amobarbital(amytal) injected into left carotid artery 
• if patient (a few seconds following of the injection) becomes speechless, the anesthic was injected into the dominant hemisphere
• test usually performed brior to ablative surgery for epilepsy and sometimes prior to tumor resection
• aim is to determine which side of the brain is responsible for certain vital cognitive functions, such as speech and memory
• cerebral dominance can also be determined by less invasive(less definitive) tests involving positron emission tomography, fMRI, or transcranial magnetic stimulation

Electroencephalogram

(EEG)

• measurement of generalized activity in the cerebral cortex
• EEG is a scalp surface recording of the algebraic summation of the excitatory postsynaptic potentials (microvolts) in the cerebral cortex
• represent the voltage recorded btw 2 electrodes applied to the scalp (19 standard possitions)
• each neuron generates a small negativity(local neg pot) on the superficial end of the neuron with respect to deeper cortical regions (every neuron works as a two pole battery)
• if inputs are irregular(not synced) sum of these miniature potentials will result in very small amplitude on the EEG, if all neurons activated at same time, mini potentials will be summated and appear on EEG as large and high amplitude waves
• clinical uses: diagnostic of sleep disorders and of seizure disorders and other abnormal states

Seizure Disorder

Definitions

• seizure: brief episode of loss/disturbance of consciousness and abnormal EEG
• convulsion: a seizure accompanied by characteristic body movements
• epilepsy: recurrent episodes of seizure/convulsive activity 
• about 1% of the US population has epilepsy 

Generalized Seizure

(typical scenario)

• patients may experience an aura or hallucination a few seconds before they lose consciousness
• massive cyclic muscle movement. biting the tongue, cheeks or both is common, but attempts to prevent it usually make matters worse
• patient than remains unconscious for up to an hour and then often sleep for several hours
• on awakening, patients are aware that the seizure has occured
• attacks can begin at any age and may recur either the next day or next year or never
• frequency and duration of seizures can increase, decrease or remain constant over years

Partial or focal seizures

• begin locally (also referred to as jacksonian, temporal lobe or psychomotor seizure)
• simple: without impairment of consciousness
• depending on anatomic site, initial symptoms may be motor, sensory, aphasic, cognitive, olfactory or psychological
• complex: with partial impairment of consciousness, which may be simple at onset, followed by alteration of imparement of conscious. symptoms the same
• both may evolve to secondary generallized tonic/clonic seizures. sometimes secondary generalized is so rapid that there is no clinical evidence of partial onset, only EEG

Temporal Lobe Epilepsy

(TLE)

• common neurological disorder that illuminates the relationship btw body and mind
• most typical type of epilepsy among adults (1mil US)
• seizure consists of bizarre hallucinations, strange feelings and the symptoms typical for psychiatric diseases
• often linked to personality change(Van Gogh)
• symptoms: intense emotions, vivid memories, sensory hallucinations, sens of fear, excessive writing(hypergraphia), altered sexuality
• "like everyone else, only more so"

Absence Seizure (petit mal)

• occur during childhood
• less than 30 sec of generalized 3Hz EEG
• loss of consciousness, but their body remains in normal position
• there is no motor signs. fluttering of the eyelids and or twitching of the mouth are typical during absence seizures

Epilepsy and EEG

• people w/ epilepsy often have changes in normal pattern of brain waves, weven without seizure, whenever possible an EEG should be performed w/i 24 hours of patients first seizure
• EEG is not foolproof, some people continue to show normal brain wave patterns even after they have experienced a seizure
• EEG is unable to detect unusual brain waves if they are generated deep in the brain
• many people wo do not have epilepsy whereas they show some unusual brain activity on an EEG

Causes of Epilepsy

• an upset to the delicate balance of synaptic excitation and inhibition in the brain
• paroxysmal depolarizing shifts in seizure focus neurons
• ionic changes: increased extracellular K and Glutamate; decreased Ca, and Na
• morphological changes and glia malfunction(gliosis)

Morphological Changes and Glia Malfunction

• cause of epilepsy
• tumors and trauma
• sclerosis of tissue(especialy hippocampus(temporal lobe epilepsy))
• metabolic dysfunction(morphologically altered astrocytes can lead to an increased in extracellular potassium and glutamate)
• some astrocytes transform (altered membrane properties) into cells that fire action potentials like neurons
• infection
• vascular disease (leaky capillaries due to morphologically changed astrocytes)
• withdrawal of chronic depressant drugs, such as alcohol or barbiturates
• in many cases the cause of epilepsy is not known

Triggering seizures

• hyperventilation
• repetitive photo stimuli presented at particular rate

Treatment of epilepsy

• aticonvulsants
• reduces excitability by prolonging the inhibitory action (barbiturates and benzodiazepines)
• decrease the tendency for certain neurons to fire high-frequency action potentials (phenytoin and carbamazepine)
• surgical removal of a seizure source or preventing the spread of seizure activity from one hemisphere to another by callosotomy

Circardian Rhythm

• is the most common rhythm 
• sleep-wake cycles
• body temperature
• hormone levels and production
• urine production
• GI motility
• liver activity
• levels of cognition
• motor performance
• heart activity
• blood sugar
• concentration of potassium and sodium ions in blood
• Temperature and light affect resting rhythms

Internal Clock

• circardian rhythms are controlled by clock genes producing proteins in rhythmic patterns
• environmental factors affecting resting rhythms are temp and light
• main biological clock(internal master) is the suprachiasmic nucleus of hypothalamus (sup to optic chiasm)

BRain Circuits involved in 

sleep-awake cycle

• light activates Supr Chias Nuc thru inputs from retina and LGN of the thalamus
• SCN provides suppressive effect on the pineal gland
• pineal gland synthesizes melatonin, a sleep inducing peptide
• SCN uses hypothalamospinal pathway, activates symp chain ganglia (paravertebral ganglia) locating ventrolaterally to the spinal cord
• neurons of the sympathetic ganglia supress production of melatonin in the pineal gland
• different systems of the human body are following circardian rhythms, and many of these rhythms are coordinated with the sleep-wake cycle

Clinical Correlations for

Sleep-Wake cycle

• tumors involving the SCN cause serious sleep disorders, especially waking from sleep
• ablation of SCN extends duration of daily sleep

EEG during Awake State

• in the awake state the EEG shows beta waves with mental activity and alpha waves with relaxation when eyes closed
• EEGs during awake states show low voltage (small amplitude) and fast waves (high frequency)

EEG during Sleep

REM Sleep

• two physiological states are described with normal sleep: REM and nonREM sleep
• REM (rapid eye movt) sleep: decreased muscle tone, muscle relaxation, low amplitude, high frequency brain waves (alpha and beta) observed on EEG, dreaming, increased HR and respiration
• about 25% of sleep is REM, sometimes called paradoxical because EEG is similar to that of an awake person but is deepest sleep
• people are less likely to be awakened during  REM
• as night progresses duration of REM is increasing from about 10 min to 40 min
• learning and memory consolidation occurs, pituitary secretes bursts of growth hormone, protein syn and neural growth are facilitated
• newborn spends 50% in REM and premature 75%

nonREM Sleep

• normal adults spend about 75% of sleep in this
• charact by slow wave EEG activity
• divided into 4 stages
• depth of sleep increases w/ progressive stages, which is marked by increasingly slower EEG waves
• after reaching stage 4 the pattern reverses, causing sleep to get lighter and waves to be quicker
• process inturrupted by REM at each plateau in sleep cycle
• cycle repeated 5-6 times 
• number of cycles decreses as night progresses
• contrary to REM, nonREM cycles are changing from long to short as night progress

Stages of nonREM sleep

• stage 1: (light sleep or drowsy; easily awaken) EEG has low amplitude (voltage), theta wave activity
• stage 2: (light sleep) EEG contains spindle shaped waves (sleep spindles) and slow, high amplitude waves (k complexes)
• Stage 3: (moderate=deep sleep) increases amplitude of waves on EEG but decreased frequency (slow wave or delta sleep)
• Stage 4: (deep sleep; difficult to awaken) EEG contains slow waves (delta waves) having large amplitude 

brain structures for sleep-wakefullness

• locus ceruleus of pons- noradrenalin (NAorNE)
• raphe nuclei of medulla nd pons- serotonin (5HT)
• sympathetic chain ganglia - norepinephrine (NE)
• tuberomammillary hypothalamic neurons histamine (HA)
• basal forebrain; nucleus basalis, septal nuclei-acetycholine(Ach)
• projections can neutralize actions of sensory info coming to the cortex via thalamic relays

Neurotransmitters influence sleep

• during induction of nonREM sleep there is a general decrease in firing of ACh, 5HT, NE, and HA neurons causing less neurotransmitters to be released
• in general the amines decrease more than ACh which leaves a dominance of ACh
• during REM sleep, the firing rate of NA neurons of locus ceruleus, 5HT neurons of raphe nuclei, and HA neurons of the tuberomammillary nucleus decrease considerably
• some ACh neurons increase firing to thalamus and cortex and suggest that ACh may induce REM sleep
• during both nonREM and REM the level of ACh is high relative to other NT but the difference is much greater during nonREM

drugs altering sleep

• by changing the relative activity of the inputs in any of the sleep states or
• by changing when the different sleep states will begin
• insomnia will ensue if, during the waking state, the aminergic inputs is increased relative to the cholinergic input
• contrast, hypersomnia occurs when there is increased cholinergic activity relatively to the aminergic activity

Insomnia

• difficulty falling asleep and/or inability to sleep (staying asleep)
• insomnia can arise from stress, jet lag, drinking too much coffee, working night shifts
• more serious insomnia can arise from psychiatric disorders such as depression

Sleep Apnea

• is interrupted breathing several seconds to more than a minute during sleep
• people suffering from apnea wake up many times thru out night, have little or no slow wave sleep, spend less time in REM sleep
• waking up from sleep apnea: airway collapses during breathing, airflow is blocked, level of oxygen in blood decreases and CO2 increases, high CO2 level causes a sudden reflex inspiration, which wakes up the individual
• in high risk idividuals it may lead to death because of respiratory arrest, underlying causes of sleep apnea are not well understood

Restless legs syndrome

• defined by unpleasant crawling, prickling or tingling sensations in one or both legs
• these sensations force individuals to constantly moe their legs to obtain relief
• as a result, such individuals have fragmented sleep at night
• underlying causes of this problem are not well understood

Narcolepsy

• the best understood sleep disorder, affecting about 250,000 people in the US
• experience frequent REM sleep attacks (30 seconds to 30 minutes) during the day
• during one of these attacks, patients go directly into REM sleep bypassing the nonREM state
• disorder is caused by a gene mutation
• methylphenidate(ritalin) or amphetamines are effective narcoleptic treatment

Memory

• ability to store, retain and recall information
• process some way is similar with a process of learning
• during the process of memory formation(learning) brain circuits undergo functional and morphological remodeling(plasticity)

procedural memory

• learned skills that are incorporated into the mind that an be recalled subconsciously (walking, riding a bicycle)
• generally not available to consciousness
• brain structure most tighly linked to procedural memory is cerebellum
• motor skills, associations, priming cues and puzzle solving skills

Declarative memory

• conscious recall of experiences, facts, or events
• mechanism underlying declarative memory has three major compenents: aquisition short term and consolidation proess), storage (long term), and retrieval
• declarative memory is more language oriented and is also subject to failure to retrieve information (forgetting)
• daily episodes, words and their meanings, history

Temporal categories of memory

• immediate memory (fractions of a second): has very large capacity, modality specific(auditory, visual, somatosens, etc)
• working memory (short term memory) (seconds to minutes)
• long term memory (hours to lifetime)

Working Memory (short term memory)

• seconds to minutes
• search for a lost item, or holding a telephone number while dialing
• needs to be rehearsed to persist
• largely depends on attention
• not linked to a specific sensory modality 

Long Term memory

• hours to lifetime
• disrupted by biochemical manipulations
• protein synthesis blockers prevent long term memory formation
• long term potentiation (LTP and long term depresssion

Memory Consolidation 

• memory consolidation is the process of transferring information from the immediate and short term memory into the long term memory
• this process sometimes requires immediate or working memory as intermediares
• the information can be stored directly into long term memory

Memory Priming

• priming is a memory effect in which exposure to a stimulus influences a response to a later stimulus
• it can occur more often following persistent stimulus repetition
• priming effects may happen even if the primer is not consciously perceived 
• primers often influence our decisions in spite of the fact that we might be unaware of their effect
• priming is resistant to brain injury or aging
• good examples of priming are commercials seen on tv

association for memory

• when we experience a new event, we relate that with another even that is already in our minds
• this process is known as association
• due to the association process we can memorize much more information when stimuli are presented in a meaningful context
• mnemonics is an example
• motivation also has an impact on memory formation (hungry people memorize food better)
• practice is an effective way to enhance our memory
• a normal adult can memorize an average of 7(+-2) numbers 
• however practicing daily for one hour over several months may improve your memory to the 80th digit threshold

Brain systems for

declarative memory

• hippocampal formation is absolutely required for long term memory consolidation
• anterior and dorsomedial nuclei of the thalamus, fornix, mammillary body, cingulate cortex, and septal nuclei also play a role in declarative memory
• storage of declarative memory takes place in cerebral cortex
• brain employs multiple modality-specific storage, cortical lesions cause fine memory for one sense but deficits in memory for another

Henry Gustav Molaison

• memory impaired patient who was widely studied
• had severe epilepsy which made him unable to work
• during brain surgery lost 2/3 of his hippocampus in both hemispheres
• suffered from severe anterograde amnesia
• Dr had to introduce himself every time they met
• his working memory and his ability to form long term procedural memories was intact
• he could learn new motor skills, despite not remembering he learned them

Brain Systems for Procedural

(nondeclearative) memory

• major brain structures responsible for procedural memory are the basal ganglia, prefrontal cortex, amygdala, sensory association corticles and cerebellum
• perceptual priming requires normally functioning sensory modality-specific associatino cortex
• interaction btw the basal ganglia and prefrontal cortex play a critical role in learning new complex motor skills
• patients with huntington's disease shows significant atrophy of the caudate and putamen and they also exhibit deficiency in motor skill learning

Korsakoff syndrome

• condition caused by thiamine deficiency that is typically associated with chronic alcoholism
• degeneration of memory-related brain structures such as mammillary bodies, hippocampal complex and the dorsomedial thalamic nucleus is typical for patients with korsakoff syndrome
• usually a treatment involving thiamine and proper nutrition is sufficient
• in severe cases, drug therapy is recommended
• if treatment is successful, improvement will occur within two years although recovery is often incomplete

anterograde amnesia:

• memory is disturbed or lost
•  inability to memorize new things, 
• a person may forget information (people, faces, names or events) after a few seconds or minutes because information does not transfer from short term memory into permanent long-term memory

Retrograde amnesia

• loss of pre-existing memories fro recollection
• the person may be able to create new memories about events that occur after the onset of amnesia but is unable to recall some (partial retrograde amnesia) or all of their life prior to the onset (complete retrograde amnesia)

Memory and aging

• overall production of acetycholine in brain decline with aging (important for learning and memory
• many memory problems experienced by older people can be lessened or reversed
• patients were able to make signif improvements in memory when given rewards and challenges
• physical exercise and mental stimulation also can readily improve mental function
• important point to remember is that as you age, you may not learn or remember as quickly as you did when you were in school but when you learn you will likely remember nearly as well
• in many cases, an older persons brain may be less effective because of a structural or organic probelm but simply as a result of lack of use

Tolerance

• escalation of dose to achieve/maintain physiological effect
• tolerance can lead to overdose because tolerance to the reward effect does not mean tolerance to negative side effects such as hyperthermia or arrhythmia

Sensitization

• opposite of tolerance
• smaller amount of the drug achieves the same effect
• has been observed for psychostimulants

Dopamine Hypothesis of addiction

• primary mesolimbic pathway is Ventral tegmentum(VTA) in midbrain via the medial forebrain bundle to nucleus accumbens
• VTA also connects to amygdala, hippocampus and medial prefrontal cortex 
• from VTA to nuc accumbens, the NT is dopamine
• drugs alter the neuromodulatory influence of dopamine on processsing reinforcement in nuc accumbens and VTA
• drugs will either prolong dopamine action in nuc accumbens or potentiate the activation of neurons in nuc accumbens and VTA

Dopamine and Addiction

• reward predictor: highly active with unexpected reward, no activity with no reward
• inceptive salience: dopamine is less a reward than the motivator

Insula and addiction

• association area with role in tying behavior and environment to active reward
• smokers with insular damage can quit smoking with ease

Drug factors

• psychoactive properties (potency)
• kinetic properties: speed of brain entry (IV v. IO v. smoke, snort)
• purity of drug: coca leaves vs IV heroin
• pharmacokinetic or pharmacodynamic tolerence
• pharmacokinetic tolerence: barbiturates 

Class I Mechanism

of drug abuse

• bind to G-protein coupled receptors on GABAergic interneurons that modulate dopaminergic neurons in Ventral Tegmentum
• includes opiods, THC, GHB (y hydroxybutyric acid)

Class II Mechanisms

of Drug Abuse

• interact with ion chennels on GABAergic interneurons and dopaminergic neurons in Ventral tegmentum
• includes benzodiazepines, nicotine, ethanol 

Class III Mechanisms of

Drug Abuse

• affects dopamine transporter function, either by competition for dopamine uptake or blockage
• includes cocaine, amphetamine, methamphetamine (ecstasy) 

Phencyclidine

• in a class of its own for mechanisms of drug abuse
• binds within the NMDA receptor, blocking ion flux

Opiod cellular and molecular adaptions

• short term opiods and similarly acting drugs lower cAMP levels and decrease firing rates acutely
• chronic administration leads to a compensatory increase in cAMP levels and subsequent hyperexcitability of nucleus accumbens
• persistent changes in transcription factors and gene expression mainting the chronic drug state
• CREB  and DeltaFosB contribute to drug induced changes in gene expression
• CREB mediates tolerance and dependence
• DeltaFosB mediates prolonged sensitization to drug exposure and may contribute to the increased drive and motivation for drug

Opiates

• include the alkaloids from the opium poppy, papaver somniferum
• opiods are compounds with opiatelike actions, including synthetic and endogenous opiods
• bind to mu-opiod receptor (MOR) located on GABA inhibitory neurons that synapse on dopaminergic neurons in VTA
• MOR is GPCR whose activation can lead to 1) reduced calcium influx and lower GABA release and 2)increased potassium efflux (hyperpolarization) and reduced neuron firing

Cannabinoids

• active ingredient in marijuanna is THC
• partial agonist of CB1 endocannabinoid receptor
• this is a GPCR that inhibits AC
• limits cAMP levels and reduces the release of GABA or glutamate from neurons that congerge on VTA

Amphetamine

• compete with dopamine for uptake into neurons by the dopamine transporter, leaving more dopamine in the synaptic cleft 
• once inside the cell amphetamine can block the packaging of dopamine into synaptic vesicles by blocking the vesicular monoamine transporter

Cocaine

• blocks the dopamine transporter, increasing the amount of dopamine in the synaptic cleft 

Phencyclidine

• PCP binds directly to a site within the NMDA receptor
• its binding prevents the receptor from allowing any ions (K, Na, Ca) from passing through the receptor channel

Ectasy/Methamphetamine

• like amphetamines, methamphetamines compete with dopamine for uptake into neurons by the dopamine transporter, leaving more dopamine in the synaptic cleft
• methamph has a higher affinity for the serotonin transporter than the dopamine
• contributes to increased 5-HT in synaptice cleft
• once inside cell it blows vesicular monoamine transporter that packages dopamine into vessicles
• monoamine accumulation eventually cause the DA and 5HT transporter to work in reverse, spilling NT into the synaptic cleft

Treating Addiction 

• block ability of drug to reach its target
• mimic drug action
• influence the process of addiction
• cognitive behavioral intervention
• contingency management intervention

blocking ability of drug to reach its target

• naltrexone antagonizes opioid receptors
• hypothetical drug interferes with cocaine actions on the DA transporter

Mimic Drug action

• sustained activation of opiate receptor by theadone
• activation of DA receptors (DAR) by various agonists or partial agonists
• nAchR binding by nicotine 

Influencing the process of addiction

• baclofen, GABA-R agonist, to reduce drug craving
• perturb glutamate rceptors (AMPA, NMDA)
• perturb host of post-receptor signaling proteins (cAMP, Ca and MAP kinase pathways) implicated in addiction
• antabuse for acloholics causes acetaldehyde to build up leading to nausea, vomiting, sweating, flushing, palpitations