Drug Addiction
OPIATES
Introduction
• Brief history
• Neurotransmitters Affected
• Brain Regions Affected
• Tolerance, Withdrawal, Behavior
Brief History
• Opiates are drugs derived from the poppy
plant
• Have been used for centuries to relieve pain
• Includes: opium, heroin, morphine, and
codeine
• Opiates such as morphine and codeine used
for medicinal purposes, however can be
abused just like opium and heroin.
History
Continued
• Opiates also inhibit brain centers controlling
coughing, breathing, and intestinal motility. Both
morphine and codeine are used as pain killers, and
codeine is also used in cough medicine.
• Opiates depress nerve transmission in sensory
pathways of the spinal cord and brain that signal
pain. This explains why opiates are such effective
pain killers.
Neurotransmitters
Various Receptors and NTS’s:
• GABA
• Endorphins
• Dopamine
• Opiate Receptors
Neurotransmitters
• Opiates bind to so-called mu (µ) receptors
• These G-protein-coupled receptors are
located on the subsynaptic membrane of
neurons involved in the transmission of pain
signals.
Neurotransmitters
GABA
• Affects dopaminergic cells
• Opiates and opioid NTS’s activate the presynaptic
opioid receptors on GABA neurons
• This inhibits the release of GABA in the VTA
• Inhibiting GBA allows the dopaminergic neurons
to fire faster
Neurotransmitters
Endorphins
• Called natural opiates
• Involved in glucose regulation
• Endorphins and Enkephalins are natural
neural peptides that bind to opiate receptors
to produce euphoric effects
• Released by brain when exposed to opiates
Neurotransmitters
Dopamine
• Dopaminergic cells- dopamine is manufactured,
transported down the length of the neuron, and
packaged for release in the synapse
• Key involvement in opioid reward
• Ventral Tegmental Area known area for DA
activity
• Opioids in VTA have a rewarding affect
• Effects of opioids are contingent on dopamine
activation
Neurotransmitters
Animal Studies
Dopamine
• (Agmo et al. 1990)
Opioids have an evolutionary purpose
• Male rats used and partnered with copulatory
females
• Rays administered nalexone, a synthetic opioid
• It is suggested that release of endogenous opioids
renders ejaculation rewarding
• Dopamine thus seems to be of slight importance
for that effect of copulation
Neurotransmitters
Dopamine
• opiates applied to the VTA increases dopamine activity.
• dopamine affects the rewarding properties of opioids in the
VTA
• morphine enhances the firing frequency of mesolimbic DA
neurons projecting from the VTA , which provides
evidence that opioids have an excitatory affect on
dopamine.
• Dopamine antagonists, molecules that bind to the receptor
and prevent it from being activated, block the effect of
opioids by halting morphine-induced activities
Neurotransmitters
Opiate Receptors
• Presynaptically inhibit transmission of
excitory pathways
• Pathways include acetylcholine, the
catecholamines, serotonin, and substance P*
*Substance P is a neuropeptide active in neurons which
mediate our sense of pain
Neurotransmitters
Opiate Receptors
• Proteins found in the brain, where naturally
occurring opioids bind to (i.e..endorphins)
• Opioids mimic these naturally occurring opioid-
like molecules that are made and used in the brain
• Four types of opiate receptors: mu, delta, epsilon,
kappa
Naltrexone, an opioid blocker that is being used for addiction
Brain Regions
Localization of Opiate Binding sites
The VTA includes
• accumbens
• caudate nucleus
• thalamus
Brain Regions
Opiates binding to opiate receptors in the NAC: Increase
dopamine release
3 neurons in opiate
action
• Dopamine terminal
• Postsynaptic cell
• Other
terminal(GABA)
The Neural Circuit
The Reward Pathway
Major structures
• the ventral tegmental
area
• the nucleus accumbens
• prefrontal cortex
Other areas include
• arcuate nucleus
• Amygdala
• locus coeruleus
• periaqueductal gray area
Tolerance
• Tolerance can be defined as the decreased potency of a
drug, such that progressively larger doses must be used to
achieve the same effect
• Dependence, which is closely associated with tolerance,
involves a continued need for opioid administration in
order to prevent withdrawal symptoms
• symptoms include nausea, gastrointestinal disturbances,
chills, and a general flu-like state in humans
• Lesion studies indicate that no single brain structure is
responsible for the withdrawal symptoms
Withdrawal
• (Caille et al. 2003)
Opiate withdrawal has been correlated with
decreased extra-cellular dopamine levels in
the nucleus accumbens (NAC) of morphine-
dependent rats. The authors tested the
hypothesis that DA transmission plays a
critical role in the induction of motivational
and somatic withdrawal symptoms.
Behavior
• Opiates and other neurotransmitters affect behavior
and feelings by opening and closing ion channels that
control the firing of nerves
• The drug produces relaxation, relief of pain and
anxiety, decreased alertness, impaired coordination
and serious problems with constipation.
• Continued use may result in weight loss, mental
deterioration and death.
• Withdrawal sickness will occur if the drug is
discontinued. Overdose can result in stupor, coma and
death.
Studies
Future Implications
• (Segall et al. 1989) found that when
naloxone was administered, eating palatable
foods was effectively decreased.
• Shows possible reward systems for anorexia
that reaffirm the behavior
• important implications for the use of opioid
antagonists in weight-loss programs
Conclusion
• One of the most detrimental side effects of opium is
addiction
• Opium addiction occurs very rapidly, sometimes within
weeks
• Continued use of the drug occurs not only for the
purpose of intoxication, but too avoid the painful side
effects associated with withdrawal that naturally come
with opiate addiction
• Thus, more studies should be done on synthetic opiates
(I.e. naloxone) in order to aid in overcoming addiction
Interesting Fact
Unlike the information portrayed in the
popular sitcom Seinfeld
You would have to ingest 10 lbs. of poppy
seeds in order to feel any opiate like effects,
or even test positive for drugs such as
heroin