addiction and opioids 2

nuculeus accumbens

this is respsobile for reward/pleasure. This is why we like substances

ventral tegmental area

this is respsosible for desire. This is why we want to use substances.

Pre frontal cortext

this is resposible for higher level functioning decesion making. makes us not like negative consqueneces

when an individual engages in. a behavior that is associated with pleasure like drugs or alcohol

the brain releases flood of neurotransmitters, specfically dopamine, in the reward center of the brain this leads to feelings of pleasure and euphoria

addiction

is a chronic relapsing disorder characterized by compulsive reward seeking despite adverse consequences

repeated exporure to drugs or alchool over time leads to changes in the brains reward system

Specifically in the structure and function of certain areas such as the ventral striatum, the prefrontal cortex, and the amygdala

MOR (MU)

euphoria, analgesia, respiratory depression

KOR (KAPPA)

dysphoria, stress like responses

DOR (DELTA)

mood modulation, some analgesia

Grpoteins are

heterotrimeric proteins located in the intracellular space

3 different subunits
alpha, beta, gamme

the alpha subunit

is attatched to plasma by membrane by lipid anchor,
binds to GDP or GTP

beta subunit

held by alpha and gamma, can be released from alpha subunit when activated

gamma subunit

attached to plasma membrane by lipid anchor

receptor proteins

aka seven transmembrane receptors cross the plasma membrane 7 times

when the signaling moleculre ligand binds to a receptor

the entire protein goes through a confirmation change

ligands examples for gprotein include

dopamine, serotonin, vasopressin, epinephrine, prostglandins, oxytocin, follicle-stimulating hormones, ETC

when G proteins are active

the alpha subunit seperates from beta and gamma subunits

alpha subunit will continue

to alter cytosolic second messangers

the beta and gammma subunits alter

plasma membrane proteins

G alpha type s (Gs)

stimulates adenly cyclase (AC) to make cylic adenosine monophasphate (cAMP). This tends to activate down stream proteins

Ga type i (Gi)

inhibits AC to make cAMP. This to inhibit downstream proteins

Ga type q (Gq)

activates PIP2/IP3/DAG pathway. This increases cytosolic Ca2+ levels

all three opioid receptors use

Galpha I

the opiod receptors are in different. parts of the brain this causes

their effects to be in different

MAT disadvantages

requires close medical supervision at a certified facility

powerful medications used may have undesirable side effects

provide potential for misuse or abuse

risk of trading one addiction for another

under physiological conditions opiod receptors are stimulated by endogenous

opioid peptides that include beta-endorphin, enkephalins and dynorphins

distributed throughout the nervous system

opioid peptides and receptors reduce responses to painful stimuli and stress, and influence reward processing and mood

binding of an extracellular signal molecule to a GPCR changes

The conformation of the receptor, which allows the receptor to bind and alter the conformation of trimeric G protein

Function: How GPCR Activation Works

1. Ligand binds receptor → receptor changes conformation

2. This allows the receptor to bind and alter the conformation of a trimeric G protein

Once active:

The α subunit separates from β and γ

α subunit alters cytosolic second messengers

β and γ subunits alter plasma membrane proteins