Week 11 - Drugs of Dependence Flashcards
physical dependence
occurs when pharmacological adaptation leads to tolerance – in which more drug is needed to achieve the same effect.
If the drug is stopped, physical withdrawal symptoms emerge, due to adaptations being transiently experienced in the absence of drug. If there are withdrawal symptoms, there is physical dependence
psychological dependence
may also lead to involves emotional-motivational withdrawal symptoms – many daily drug users show both dependences.
addiction
occurs in a small minority of people who initiate drug use – addiction
leads to compulsive and out-of-control drug use as a component of physical dependence.
Origins of substance dependence
Many variables work simultaneously to influence the probability and likelihood that a beginning user will develop physical/psychological dependences and/or an addiction to a compound.
Generally speaking, these variables can be organized into three categories:
agent (drug), host (user), and the environment in which use occurs.
Reinforcement is the ability of drugs to produce effects in the user which make reuse more likely and desirable.
The more reinforcing the drug is, the more likely the user will seek to re-use, possibly leading to abuse.
Drug dependence
- brains reward mechanisms produced slight mood elevation to intense pleasure
- D2 receptors are involved in the reward dimension of addiction but not withdrawal aspects
- genetics play a role in susceptibility to addiction
Innate tolerance
genetic lack of sensitivity observed in first-time use (?)
Acquired tolerance
Acquired tolerance develops due to prolonged exposure to a drug.
pharmacokinetic (change in distribution and metabolism), and pharmacodynamic (regulation of receptor numbers)
Acute tolerance
a process whereby the brain and central nervous system enact processes to immediately mitigate the effects of a given substance
a decreasing drug effect relative to drug-plasma levels (DPL) over a period of minutes to a few hours
Reverse tolerance
in response with repeated use
basically instead of becomign tolerant to the same dose of a drug over time, your body react more (reponse wise)
Cross tolerance
repeated use of one drug affects tolerance of other drug classes
Animal Drug Models
Generally, animals are good models of self-administration of drugs with positive effects.
Dopamine is released in the nucleus accumbens when a rat presses a lever that delivers reinforcing brain stimulation to its ventral tegmental area (VTA)
Physical reward pathways in the rat and human brain
reward pathways:
dopamine released from brain’s mesolimbic system. System comprises of nucleus accumbens where reward perception and reinforcement occur, and the (VTA) ventral tegmental area is reponsible for dopamine production, and thw prefrontal cortex governs decision making.
When activated by pleasurable stimulu, the pathway triggers c cascade of responses motivating individuals to seek out repeating the experiences.
- the mesolimbic tract including the ventral tegmental area (VTA), the nucleus accumbens, and the frontal cortex.
- Collateral communication also occurs to the amydala and hippocampus such that affective and memory systems are impacted, and 5-HT, glutamate, NA, GABA and endogenous opioids may play roles as well.
In animals and humans many abused substances share one
physiological effect:
an increase DA release in the
nucleus accumbens.
Drugs which block DA receptors in this region can generally produce bad feelings – dysphoria.
dopamine D2 receptor in the nucleus accumbens
seems to be key
Transgenic mice without D2 receptors do not demonstrate reward properties of morphine administration;
Interestingly, these animals still went through physical withdrawal syndrome…
This suggests that the D2 receptors are involved in the reward dimension of addiction, but not the withdrawal aspects.
How does the brain cope with change?
The CNS has “plasticity” in that it can
modify its hardware to best function
in a changing environment.
This change in receptor numbers is
profoundly sensitive to the presence
of CNS drug, depending upon the
concentration used and time period of treatment.
