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Samenvatting Neuropsychology and Psychopharmacology
- Établissement
- Katholieke Universiteit Leuven (KU Leuven)
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INTRODUCTION TO DRUG ACTION AND ABUSEDrug mode of action
Both pharmaceuticals and illegal drugs have several basic modes of action.
Pharmaceutical drug Basic mode of action
Alprazolan (Xanax), diazepam (Valium) Increase GABA
/ Anti-anxiety drugs
Fluexetine (Prozax), paroxetine (Paxil, duloxetine Allow norepinephrine and/or serotonin to accumulate at the
(Cymbalta) synapse, which explains their effectiveness as anti-depressants
/ Anti-depressants
Drugs used for Alzheimer (memory loss) Allow ACh to accumulate at synapses in the limbic system
Antipsychotic drugs Decrease the activity of dopamine
Caffeine Keeps us awake by interfering with the effects of inhibitory NT
in the brain
Opiates (codeine, heroin, and morphine) Bind to endorphin receptors and reduce in this way pain and
produce a feeling of wellbeing
Drug abuse is linked to neurotransmitter levels
The brain’s reward system rewards and motivates us to do those behaviors that help us survive. When
people abuse drugs or alcohol, they also stimulate the reward system of the brain, which promotes drug-
seeking and addictive behavior. Drugs of abuse, including alcohol, involve an influx of dopamine in the
nucleus accumbens (NA) in the brain’s reward center, which produces the pleasurable feelings or ‘high’
that results from drug or alcohol use. While all drugs of abuse increase dopamine levels in the reward
pathway, not all drugs increase dopamine in the same way. Some drugs contribute to increasing
dopamine levels by blocking reuptake through their effect on certain NT (serotonin, endorphins and
GABA), while others can directly stimulate the release of dopamine.
The brain’s reward circuit is part of the limbic system, and includes the following structures: VTA, NA and
substantia nigra, and links together brain structures that control and regulate pleasure in the brain. The
majority of drugs of abuse act on dopamine levels in either the NA or the VTA. The amygdala is
responsible for integrating emotional respnses, behavior and motivation. The hippocampus plays a role in
memory function.
Drug of abuse Interaction with the brrain’s reward circuit
Alcohol Acts as a depressant by increasing the action of GABA (an inhibitory NT), which lead to a
feeling of relaxation, lowered inhibitions, impaired coordination, slurred speech, …
Nicotine Causes a release of epinephrine, increasing blood sugar and causing the initial feeling of
stimulation, but after blood suger falls, depression and fatigue set in, causing the user to
seek more nicotine.
Cocaine and crack Is a powerfull stimulant in the CNS that interferes with the reuptake of dopamine at
synapses, increasing overal brain activity, causing a short rush of well-being (more active
brain), while long-term use of cocaine causes a loss of metabolic function in the brain (less
active brain). With continued use, the brain makes less dopamine to compensate.
Methamphetamine Is a powerful CNS stimulant, structure is similar to that of dopamine. Has sedative side
and ecstasy effects, and are therefor known as date rape or predatory drugs.
, Heroin (opiates) Binds to receptors that are meant for the endorphins. With repeated use, the body’s
production of endorphins decreases. Tolerance develops, so the user needs to take more of
the drug just to prevent withdrawal symptoms, and the orginal euphoria is no longer felt.
Marijuana and K2 Binds to a receptor for anandamide, causing mild euphoria along with alterations in vision
and judgement .
PRINCIPLES OF PSYCHOPHARMACOLOGY
Grouping psychoactive drugs
Groups of psychoactive drugs
I. Antianxiety agents and - Increasing doses of sedative-hypnotic and antianxiety drugs affect
sedative-hypnotics behavior: low doses reduce anxiety and very high doses result in death
- Benzodiazepines (diazepam, - Cross-tolerance: reduction of response to a novel drug because of
alprazolam, clonazepam) tolerance to a chemically related drug
- FASD: range of physical and intellectual impairments observed in some
- Barbiturates and alcohol
children born to alcoholic parents
- Other anesthetics (GHB, Special - Drug effects at the GABAA receptor: sedative-hypnotics act at the
K/ketamine, PCP/angel dust) barbiturate site, and antianxiety agents act at the benzodiazepine site.
Taken together, these two types of drugs can be lethal.
II. Antipsychotic agents - Dopamine hypothesis of schizophrenia: idea that excess dopamine
- First generation: chlorpromazine, activity causes symptoms of schizophrenia
haloperidol - FGA’s act mainly by blocking the dopamine D2 receptor
- Second generation: clozapine, - SGA’s weakly block dopamine D2 receptors, but also block serotonin 5-
HT2 receptors
aripiprazole
- Drug effects at D2 receptors: the antipsychotic agent chlorpromazine can
lessen schizophrenia symptoms, and amphetamine or cocaine abuse can
produce them. This suggests that schizophrenia is related to excessive
activity at the D2 receptor.
III. Antidepressants and mood - MAO inhibitor: antidepressant drug that blocks the enzyme monoamine
stabilizers oxidase from degrading such neurotransmitters as DA, NE and 5-HT
- Antidepressants - Tricyclic antidepressant: FGAD; its chemical structure is characterized by
- MAO inhibitors three rings, blocks 5-HT reuptake transporter proteins
- SGAD: Drug that acts similarly to tricyclics but more selectively on 5-HT
- Trycyclic antidepressants
reuptake transporter proteins
- SSRI’s: fluexetide, sertraline, - SSRI: tricyclic antidepressant drug that blocks 5-HT reuptake into the
paroxetine presynaptic terminal
- Mood stabilizers (lithium, sodium - Drug effects at 5-HT receptors: different antidepressant drugs act on the
valproate, carbamazepine) serotonin synapse in different ways to increase its availability
- Mood stabilizers: drug for treating bipolar disorder; mutes the intensity
of one pole of the disorder; making the other pole less likely to recur
IV. Opiod analgesics - Endorphin: opiod peptide that acts as a neurotransmitter and may be
- Opium derivatives (morphine, associated with feelings of pain or pleasure; mimicked by opiod drugs such
codeine, heroin) as morphine, heroin, opium and codeine
- Endogenous opoid neuropeptides - Competitive inhibitor: drug, such as nalophrine and nalozone
(antagonists), that acts quickly to block action by competing with the
(enkephalins, dynorphins,
opioid for binding sites; used to treat opiod addiction
endorphins) - Potent poppy: opium is obtained from the seeds of the opium poppy;
morphine is extracted from opium, and heroin is in turn synthesized from
morphine
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