Pharmacology of Reward Flashcards
What brain structures are thought to comprise the brain reward pathway?
The ventral tegmental area, the nucleus accumbens, amygdala, hippocampus, lateral hypothalamus, and prefrontal cortex
What role do the ventral tegmental area and nucleus accumbens play in the reward pathway?
The VTA and NAcc are the interface between limbic-emotional-motivational input and extrapyramidal regulation of motor behavior.
What role does the amygdala play in the reward pathway?
The amygdala is the key integrative structure for forming stimulus/reward pathways
What role does the hippocampus play in the reward pathway?
The hippocampus is a memory circuit involved in mediating associations between biologic stimuli (or drugs of abuse) and environmental cues.
What role does the prefrontal cortex play in the reward pathway?
Certain regions of the PFC are critical for executive function in providing control over impulses from destructive behavior. Their impairment following chronic drug abuse appears to be an important mediator in the loss of control over drug intake.
Where are the dopaminergic neurons located in the reward pathway?
Dopaminergic neurons are located in the Ventral Tegmental Area and extend to the Nucleus Accumbens via the Mesolimbic Dopamine Pathway.
In general terms, how does the brain dopamine system function in learning physiologically relevant behaviors?
The normal function of the pathway is to mediate pleasure/reward and strengthen behaviors associated with natural reinforcers suck as food, water, and sexual contact.
What is a “reward”?
A reward is a stimulus that the brain interprets as intrinsically positive or something to be approached. Drug induced pleasurable states are important motivators of initial drug use. A reinforcing stimulus is one that increases the probability that behaviors paired with it will be repeated.
In general terms, how do drugs of abuse interact with the brain reward pathway in the Reactive Reward System?
Drug induced increases in dopamine transmission in the NAcc and Amygdala results in pathological “learning” which triggers drug seeking behavior when presented with internal cues (craving, withdrawal) or external cues (environmental associations with past drug use).
How does the amygdala function in the reactive reward system?
Once learning has been conditioned in the amygdala, connections back to the VTA act as a detector for anything relevant to previous drug abuse experience. Projections from the amygdala to nucleus accumbens initiate impulsive-automatic-obligatory actions to find and take more drugs. Akin to a reflex action.
What is the reflective reward system?
The reflective reward system is a complementary and potentially competitive component of the reactive reward system with connections to the prefrontal cortex and nucleus accumbens.
How does the reflective reward system develop and how does it influence actions?
The system is built over time with influences from genetics, neurodevelopment, experience, peer pressure, and learning social rules and can focus the final output of the reward system into beneficial long term goal directed behavior. The balance between the reflective and reactive reward systems determines whether the output will be short-term rewards (drug seeking) or long-term rewards (beneficial behavior)
How does compulsive drug use develop?
Repetitive drug-induced reward experiences alter the reward circuits such that not only will drug ingestion cause mesolimbic dopamine release, but also cues that merely predict pleasure will have the same effect.
The amygdala has also learned that these cues signal a relief from craving.
Cues cause DA release in NAcc which then triggers GABAergic release from NAcc -> Thalamus -> prefrontal cortex.
Absence of Reflective reward system allows reactive system to dominate and cause drug seeking behavior.
What pharmacokinetic properties increase the abuse liability of a drug?
Reinforcing properties: All drugs of abuse cause dopamine activity in the NAcc.
Rate of onset: More rapid = more addictive
Route of Administration: Inhalation>IV>Mucous Mmbr>oral
Termination: Drugs with shorter half life are more addicting; acutely - quick offset of drug likely leads to more frequent dosing; chronically - withdrawal effects are more severe with shorter half lives (eg heroin)
What pharmacogenetics characteristics increase the abuse liability of a drug?
Drug effects vary among individuals, possibly due to polymorphisms in the genes that code for enzymes involved in absorption, metabolism, and excretion or in receptor mediated responses. This can influence innate tolerance, rate of acquired tolerance, or the likelihood that intoxication is a pleasurable feeling. (eg Asians who cannot metabolize acetaldehyde, individuals who cannot metabolize nicotine)
