Chapter 1: Neurobiology of SUDs Flashcards
Drug use alters a biological or physiological baseline or set point.
- Mesolimbic reward paths reset so that DA reduced for normal pleasurable activities. A similar reset occurs in the LC but in opposite direction, so that NE release increased during withdrawal.
- With repeated use the response to augmented DA is more numerous, strengthened inhibitory auto-receptor control which leads to decreased basal DA. DA deficiency produces dysphoria.
- Drug induced sensitization to drug-associated cues that leads to “wanting”.
Changed Set Point Model
- Those who develop SUDs have abnormalities in prefrontal cortex which compromise signaling to mesolimbic rewards system.
- PFC; regulation of judgement, planning; impulse control
- PFC sends inhibitory signals to mesolimbic system
- Repeated drug use causes further damage.
Cognitive Deficits Model
The ___ ___ ___ is linked to drug and cue inducing craving states, along with the ________ and ________ ______ ______
Orbital Frontal Cortex | Amygdala | Anterior Cingulate Cortex
These predict relapse; often observable on scans as prefrontal cortex activation.
Cravings
A second messenger, used for intracellular signal transduction, such as transferring into cells the effects of hormones like glucagon and adrenaline, which cannot pass through the plasma membrane.
Cyclic Adenosine Monophosphate | AMP
“related to dopamine” (literally, “working on dopamine”). Substances or actions that increase dopamine-related activity in the brain.
Dopaminergic
From the Inside
Endogenous
The branch of medicine which deals with the incidence, distribution, and possible control of diseases and other factors relating to health.
Epidemiology
From the outside
Exogenous
The chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. In humans, it is also directly responsible for the regulation of muscle tone.
Gamma-AminoButyric Acid | GABA
Midbrain and Cortex. Reward system consisting of brain circuits activated to a degree by all drugs associated with compulsive use.
Mesocorticolimbic Reward System
- One amino group connected to an aromatic ring by a two-carbon chain
- They serve to inactivate monoamine neurotransmitters
- Involved in numerous psychiatric and neurological diseases, some of which can be treated with monoamine oxidase inhibitors (MAOIs). Dopamine, serotonin and epinephrine are examples
MonoAmine Oxidase(s)
- Protein structures that regulate concentrations of extracellular monoamine neurotransmitters.
- Three major classes (SERT, DAT, NET) are responsible for the reuptake of their associated amine neurotransmitters (serotonin, dopamine, norepinephrine).
- Located just outside the synaptic cleft.
- Due to their significance in neuronal signaling, they are commonly associated with drugs used to treat mental disorders as well as recreational drugs.
- Compounds targeting them include tricyclic antidepressants, SSRIs (Prozac), stim-meds like Ritalin, and amph-meds (Adderall, Dexedrine etc.).
- MDMA (“ecstasy”, “molly”) and natural alkaloids such as cocaine exert effect in part by interaction with these; blocking transporters from mopping up dopamine, serotonin, and other neurotransmitters from synapse.
Monoamine Transporters | MATs
Term used in neuroscience to indicate the part of the central nervous system (brain and spinal cord) that underlies a specific behavior, cognitive process, or psychological state.
ex: “The _______ ________ responsible for tolerance and withdrawal overlap, since withdrawal only occurs in patients who have developed tolorance”.
Neural/Neurobiological Substrate
- Plays significant role in the cognitive processing of motivation, aversion, reinforcement learning, ande reward (incentive salience, pleasure, and positive reinforcement).
- Plays a significant role in addiction.
Nucleus Accumbens
Synapse
