MEDI7111 Lecture Notes - Lecture 2: Reuptake, Dopamine Transporter, Polyphagia
Mental Health 2
Drugs of Dependence
Why take drugs?
Physical dependence
oOccurs when pharmacological adaptation leads to tolerance (thus more drug is
needed to have the same effect)
oWithdrawal only occurs with physical dependence
Psychological dependence
oEmotional need for the drug/substance
oNo underlying physical need
Addiction
oCompulsive out of control drug use as a component of physical dependence
oOnly occurs in a small minority of users
Reinforcement
Reinforcement refers to the ability of drugs to produce effects in the user which make reuse more
likely and desirable. This occurs through the effects the drug has on the CNS; using the same reward
pathways as biologically crucial activities such as procreation and eating. Animal models have shown
that the ventral tegmental area, the nucleus accumbens and the frontal cortex are the main
pathways for reward however there is cross talk with the amygdala and hippocampus for the
emotional and memory associated rewards.
Many abused substances (opiates, stimulants, depressants, cannabinoids and nicotine) share one
physiological effect; increased dopamine release in the nucleus accumbens. This increase in release
obviously happens to varying degrees as each drug has a different level of addiction and reward
capacity. The D2 receptor for dopamine has been shown to be the crucial for reward from drug
taking, therefore absence/inhibition of D2 receptors results in no reward from addiction but
interestingly withdrawal is still noted, indicating that addiction pathways must still be active.
Tolerance
The CNS has plasticity in that it can modify its receptor concentration to best function in a changing
environment, depending upon the concentration used and the time period of treatment. If an
antagonist is administered, the body will respond by increasing receptor density, however if an
agonist is administered, the receptor density will decrease. This means that for a drug to have the
same effect, the dose must be increased to match the new physiological environment.
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Often tolerance is not consistent across body systems, therefore common side effects of drugs (e.g.
constipation & respiratory depression in opiates) are still present and increasingly severe as the
patient increases their dose to get the same high.
The Drug’s Abuse Risk
There are a number of factors which influence the risk of a drug to be used in an abusive fashion:
Rapidity of onset
oThe faster the drug gets to the CNS the more addictive it is
oE.g. chewing coca leaves vs IV injection
Availability
oWhere most regulation is placed
o↓ availability = ↓ likelihood of taking drug
Cost
Purity/potency
oMore potent = more addictive
Mode of administration
oNeed access to needles, pipes etc.
User/Environmental Variables
Genetic factors
oMany genes of small effect
oMay combine to strengthen the degree of reinforcement or euphoria
oInnate tolerance (e.g. better able to metabolise drugs)
Psychiatric disorders (diagnosed or undiagnosed)
oMay turn to drugs to self-medicate
oLess often it’s “I used drugs because it feels good”, more likely it’s “I use drugs to
feel less shit”
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Document Summary
Physical dependence: occurs when pharmacological adaptation leads to tolerance (thus more drug is needed to have the same effect, withdrawal only occurs with physical dependence. Psychological dependence: emotional need for the drug/substance, no underlying physical need. Addiction: compulsive out of control drug use as a component of physical dependence, only occurs in a small minority of users. Reinforcement refers to the ability of drugs to produce effects in the user which make reuse more likely and desirable. This occurs through the effects the drug has on the cns; using the same reward pathways as biologically crucial activities such as procreation and eating. Animal models have shown that the ventral tegmental area, the nucleus accumbens and the frontal cortex are the main pathways for reward however there is cross talk with the amygdala and hippocampus for the emotional and memory associated rewards.
