PSY/IPN1023 Body and Behavior
TASK 8 – LEARNING AND SUBSTANCE ABUSE
Abuse, dependence and addiction
The abuse of drugs can be divided into two patterns; deliberate abuse, by people who use a
drug for its (euphoriant) effects, and unintentional abuse, by people who begin using a drug
and end up using them inappropriately. People who abuse a drug (such as a benzodiazepine)
may become dependent, although abuse and dependency are not always mutually inclusive.
An abuser is not necessarily dependent.
Although an individual who is addicted to BDZs is usually physiologically dependent on the
medication, a patient may have a physical dependence without being addicted. Addiction
requires evidence of compulsive drug-seeking behavior and loss of control. Among
legitimate users of BDZs, physical dependence can result from long-term regular use.
Pharmacologic dependence is a natural physiologic adaptation in response to the continual
use of many drug types. This adaptation is the biological basis for pharmacologic tolerance
and withdrawal symptoms. Besides, although physiological dependence (manifested by
tolerance and withdrawal) is typical of addiction, physiologic dependence is not a required
criterion for addiction. A rapid onset of action, occurring in drugs with a short half-life, may
increase abuse potential.
Sources: Carlson (2017)
Positive reinforcement
Drugs that lead to dependency must first
reinforce people’s behavior. Most drugs of abuse
have reinforcing effects (except for
hallucinogens). That is, their infects include
activation of the reinforcement mechanism. This
activation strengthens the response that was just
made. Particularly, if the drug was taken by a
fast-acting route such as injection or inhalation,
the last response will be the act of taking the
drug, so that response will be reinforced.
Changing the route of administration can change
the abuse potential of a drug.
Do people choose to become dependent on a drug that produces pleasurable effects in the
short term but also produces powerful aversive effects in the long term? The answer is that
our reinforcement mechanism evolved to deal with the immediate effects of our behavior.
The immediate reinforcing effects of a drug can, for some individuals, overpower the
recognition of the long-term aversive effects.
Natural reinforcers have one physiological effect in common; they cause the release of
dopamine; this release appears to be a necessary (but not sufficient) condition for positive
reinforcement to take place.
,PSY/IPN1023 Body and Behavior
Drugs of abuse trigger the release of dopamine
in the nucleus accumbens (NAC). It appears
that the process of substance abuse begins in the
mesolimbic dopaminergic system and then
produces long-term changes in other brain
regions that receive input from these neurons.
The first changes appear to take place in the
ventral tegmental area (VTA).
Striatum
As a result of changes in the VTA, increased activation is seen in regions that receive DA
input from the VTA, including the ventral striatum, which includes the nucleus accumbens
(NA), and the dorsal striatum, which includes the caudate nucleus and putamen. Synaptic
changes that are responsible for the compulsive behaviors that characterize substance abuse
occur only after continued use of a drug. The most important of these changes appears to
occur in the dorsal striatum. The basal ganglia play a critical role in operant conditioning,
and substance abuse involves that.
The early reinforcing effects that take place in the ventral striatum (namely, in the NAC)
encourage drug-taking behavior, but the changes that make the behaviors become habitual
involve the dorsal striatum. An important role of the dorsal striatum is establishment of
automatic behaviors (disrupted in patients with Parkinson’s).
Connections between mesolimbic pathway and striatum
One experiment suggests that the neural changes responsible for chronic drug use follow a
dorsally cascading set of reciprocal connections between the striatum and VTA.
Altogether, the release of dopamine in the NAC leads to acquisition of the drug-taking
behavior, but changes in the dorsal striatum are responsible for the establishment of the
compulsive drug-taking habit. In addition, in individuals who abuse the drug, dopamine is
released in the dorsal striatum not by the drug itself but by stimuli associated with procuring
and taking the drug, including places where the drug was taken and people with whom it was
taken.
So when people first take a drug of abuse, they
experience pleasurable effects. If they continue to
take the drug, their compulsion to take the drug is
not motivated by the pleasurable effects, but by
drug-related cues that give rise to the urge to
perform drug-seeking behaviors.
, PSY/IPN1023 Body and Behavior
Dopamine receptors
The alterations that occur in the NAC and later in the dorsal striatum include changes in
dopamine receptors on the medium spiny neurons, which are the source of axons that project
from both of these regions to other parts of the brain. Increases are seen in dopamine D1
receptors, which cause excitation and facilitate behavior, and decreases are seen in dopamine
D2 receptors, which cause inhibition and suppress behavior. One study found that cocaine
increased the firing of the interneurons, and that inhibiting the firing of these neurons blocked
the reinforcing effect of cocaine.
Role of the prefrontal cortex
The role of the prefrontal cortex in judgment, risk taking, and control of inappropriate
behaviors may explain why adolescents are much more vulnerable to developing substance
abuse than are adults. Adolescence is a time of rapid and profound maturational change in the
brain, especially in the prefrontal cortex. Before these circuits reach their adult form,
adolescents are more likely to display increased levels of impulsive, novelty-driven, risky
behaviors. Adolescents who score low on behavioral inhibition have an increased risk of
developing substance abuse.
Some regions of the PFC have inhibitory connections with the striatum, and increased
activity of these regions is correlated with resistance to substance abuse.
People with a long history of substance abuse not only show deficits on tasks that involve the
PFC, but also show structural abnormalities in this region. Studies reported decreases in
gray matter volume of the cingulate cortex and limbic cortex of methamphetamine- and
cocaine abusers. Another study found evidence of loss of behavioral control caused by
decreased activation of the dorsomedial PFC.
The negative and cognitive symptoms of schizophrenia
appear to be a result of hypofrontality; decreased activity
of the PFC; the symptoms are very similar to those of
long-term substance abuse. There is a high comorbidity
between schizophrenia and substance abuse. One study
found that PFC gray matter volumes were lower in
patients with alcohol abuse, schizophrenia and even
lower in patients with both disorders (figure).
Orexin and MCH
Orexin (also called hypocretin) plays an important role in control of sleep stages and food-
seeking behavior. Orexin is synthesized in neurons in the lateral hypothalamus and is released
in many parts of the brain, including those that play a role in reinforcement, such as the VTA,
NAC and dorsal striatum. Administration of reinforcing drugs (or associated stimuli)
activates orexinergic neurons, and infusion of orexin into the VTA reinstates drug seeking
behavior.
