1. Ionotropic effects-attaches to the receptor causing the immediate

opening/closing of an ion gate . Fast, Short lived response, ~20ms

2. Metabotropic effects: Slow, long lived: attaches to a receptorà activation of G-proteins.

G-proteins: A protein coupled to the energy-storing molecule, guanosine triphosphate (GTP). Activates/ increases amount of

Second messenger: Chemicals that carry a message to different areas within a postsynaptic cell; can open channel, activate gene etc.

Some neurotransmitters can interact with both ionotropic and metabotropic receptors.

3. Neuromodulators: Neuromodulators do not by themselves strongly excite or inhibit a neuron, instead they alter (modulate) the effects of a neurotransmitter,

1. Acetylcholinesterase (AchE): breaks down Ach to Acetate and choline (choline recycled by presynaptic cell)

2. Serotonin and catecholamines: reuptake-- NT taken up by the presynaptic neuron which released them; occurs through specialized proteins called transporters.

3. Some serotonin and catecholamine molecules are converted into inactive chemicals

example: COMT (catechyl o methyl transferase) - converts catecholamines) and MAO (monoamine oxidase) - converts both catecholamines and serotonin).

B) How can drugs act at synapse?

By altering synthesis of neurotransmitter, disrupting vesicles, increasing /decreasing release, decreasing reuptake, blocking its breakdown or directly simulating or blocking postsynaptic receptors.

C) Affinity: How strongly the drug attaches to the receptor.

D) Efficacy: The tendency of the drug to activate a receptor.

Different people have different distribution of receptorsà different behavioral effects with same drug. Ex many kinds of Dop receptors, each with diff effect

E) Olds and Milner (1954) self-stimulation of the brain: rats will press lever for selfstimulation until they collapse with exhaustion if electrode is in certain brain areas.

Brain stimulation is reinforcing almost exclusively in tracts of axons that release dopamine, especially in an area called the nucleus accumbens. Cells located in the nucleus accumbens are inhibited by increased DA activity. Can get similar effect with decreased glutamate.

Evidence suggests that dopamine and the nucleus accumbens play an important role in attention-getting:

new food à more DA activity

foot shockà DA activity

F. Stimulant drugs (e.g., amphetamines, cocaine, etc.) produce excitement, alertness, elevated mood, decreased fatigue, and sometimes motor activity. Increase activity at dopamine receptors.

DA mostly inhibitory. Decreased background activityà higher signal to noise ratioà stimulating effect.

1. Amphetamine increases dopamine release from presynaptic terminals by reversing the flow of the dopamine transporter. (Release instead of reuptake)

2. Cocaine blocks reuptake of catecholamines and serotonin. Prolongs effects. The behavioral effects of cocaine are believed to be mediated primarily by dopamine and secondarily on serotonin.

The effects of amphetamine and cocaine are both short lived because of

a. washing away of dopamine,

b. negative feedback loop on presyn cellà decreased release à "crash" into depressed state

c. Tolerance: repeat exposure à less DA, more dynorphin (counteracts cocaine effects)

3. Methylphenidate (Ritalin): Stimulant currently prescribed for Attention Deficit Disorder (ADD); blocks reuptake of dopamine, increase 5HT release. Longer lasting and less intense, less addictive compared to cocaine. Increased attention due to DA, decreased activity due to 5HT.

Repeated use: ex: cocaineà changes in blood flow/ metabolism: stroke, epilepsy, memory impairment. MethyleneDioMethAmphetamine (ecstasy) ): destroys stimulated axons!

G. Nicotine: Compound found in tobacco. Stimulates the nicotinic ACh receptor: increases DA release by attaching to nic. receptors of cells that release dopamine in nucleus accumbens.

H. Opiate Drugs: Derived from (or similar to those derived from) the opium poppy. Common opiates include morphine, heroin, and methadone. Stimulate specific receptors. Endogenous opiates: Endorphins. Opiates have a net effect of increasing the release of dopamine by stimulating endorphin synapses. Pain relief. Central mechanismà Relieves pain in brain!

I. Phencyclidine (PCP or "angel dust") inhibits a type of glutamate receptor, NMDA receptors, in the nucleus accumbens. Unlike other abused drugs, PCP does not increase activity at dopamine synapses

J. Marijuana: Contains the chemical D9-tetrahydrocannabinol (D9-THC) and other cannabinoids. Attaches to specific cannabinoid receptors. Anandamide, 2AG : endogenous brain chemical that binds to cannabinoid receptors. Decrease pain, act on 5HT-3 receptor (involved in nausea).

K. Hallucinogenic drugs: Drugs that distort perception. Many resemble serotonin and binds to serotonin type 2 (5-HT2) receptors.

L. Caffeine: constricts blood vessels to the brain leading to decreased blood flow. Blocks presyn. adenosine receptors resulting in increased release of DA and glutamate.

M. Alcohol: Inhibits Na+ ion flow across the neuron membrane; decreases serotonin activity, facilitates transmission at the GABA-A receptor, blocks glutamate receptors, and increases dopamine activity. Mice without D2 rec prefer water to alcohol. DA involved in reinforcing value.

Virtually all reinforcing experiences including addictive drugs, sex, and playing video games stimulate dopamine receptors.

An alternate form of the dopamine D2 receptor that may be less sensitive than the usual form has been implicated in risky behaviors such as alcohol abuse, overeating, and habitual gambling. Similarly, an alternate form of the dopamine D4 receptors has been associated with a "novelty-seeking" personality.(impulsive, exploratory, quick tempered) also higher incidence of schizo

A Neurotransmitters: released next to a target cell; hormones: carried to targets throughout the body

B Hormones: Chemicals secreted by glands and carried by the blood to other organs whose activity they influence. Coordinate long-lasting changes in multiple parts of body.

C Endocrine glands: Hormone-producing glands.

D Hormonal effects similar to those of metabotropic neurotransmitters and neuromodulators. Some chemicals are both hormones and neurotransmitters.

1. Protein and Peptide hormones: Composed of chains of amino acids. Ex:Insulin

These hormones attach to receptors on the cell membrane where they activate second messengers within the cell.

2. Steroid hormones contain four carbon rings and are composed of cholesterol.

Ex: Cortisol

Can bind to membrane receptors or can enter cells and attach to receptors in the cytoplasm, which then move to the nucleus of the cell where they determine gene expression.

3. Sex hormones: special category of steroids. Released primarily from the gonads. Effects on brain, genitals, other organs.

Androgens: Testosterone and several other steroids. Levels are higher in men than women.

Estrogens: Estradiol and several other steroids. Higher in women than men.

Sex-linked genes: Genes activated by sex hormones; exert

stronger effects in one sex than the other.

Anabolic steroids: Testosterone and other androgens, and synthetic chemicals derived from them that tend to build up muscle

4. Thyroid hormones: Hormones released by the thyroid gland. Contain iodine.

5. Monoamine Hormones: Monoamines such as norepinephrine and dopamine.

1. Pituitary gland: Master Gland. Anterior and Posterior part. Controlled by hypothalamus.

Hypothalamus: makes oxytocin and vasopressin (also known as antidiuretic hormone). Transports them down their axons to the

2. Posterior pituitary gland: Composed of neural tissue. Releases the hormones which (synthesized in the hypothalamus) into blood

Six hormones of the anterior pituitary: