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Transcript
Homeostatic system
and Drugs
藥理學科E501
詹銘煥
You have to think…
 How do drugs work in your body?
 Why is your body susceptible to the influence of
drugs and other substances?
 Why do human beings like to abuse drugs?
Key Terms
 Homeostasis: maintenance of internal stability or
equilibrium
 Neurotransmitters: chemical messengers released by
neurons
 Hormones: chemical messengers released into the blood
by glands
 Endocrine system: relating to hormones, their functions,
and sources
 Neurons: specialized nerve cells that make up the nervous
system and release transmitters
Learning Objectives
 The role of receptors in mediating the effects of
drugs, hormones, and neurotransmitters.
 Distinguish between receptor agonists and
antagonists.
 Neurotransmitters associated with drug addition.
 Identify which brain areas are most likely to be
affected by drugs of abuse.
 How and why anabolic steroids are abused and the
health impact attributed to abuse?
Nerve cells (neurons)
 They can conduct bioelectric signals for long
distances without any loss of signal strength.
 They possess specific intercellular connections
with other nerve cells and with innervated tissues
such as muscles and glands.
 Neurons can send discrete excitatory or inhibitory
messages to their target cells.
How do neurons
communicate ?
Neurotransmitters
Receptors
Electric transmission
Chemical transmission
Common neurotransmitters
Acetylcholine: mild euphoria
Norepinephrine: excitation
Epinephrine: excitation
Dopamine: euphoria
Serotonin (5HT): aggressiveness
GABA (gamma-aminobutyric acid): sedation
Endorphins: mild euphoria, blockade of pain
Plasma membrane
The membranes of cells (3-6 nm) are
effectively impermeable to ions and polar
molecules.
Receptors
Receptors: proteins inserted in the plasma
membranes of cells.
They permit external chemical signaling
molecules, the first messengers, to direct
the activities of cells in a variety of ways
with high specificity and precise control in
terms of extent and duration.
Key Terms
 Opiate receptors: receptors activated by opioid
 Endorphins: neurotransmitters that have narcoticlike effects
 Agonist: a type of substance that activates a
receptor
 Antagonists: a type of substance that blocks a
receptor
 Neurons: specialized nerve cells that make up the
nervous system and release transmitters
Neurotransmitters in brain-Drugs of abuse
Acetylcholine: tobacco, nicotine
Dopamine: amphetamines, cocaine
Endorphins: narcotics
GABA: alcohol, diazepam, barbiturates
Serotonin: LSD (lysergic acid diethylamide)
The PRP includes the dopaminergic pathway from the
ventral tegmental area (VTA) to the nucleus accumbens (NA)
and extending to the prefrontal cortex. Dopaminergic
pathways are activated by the neurotransmitter, dopamine.
The serotonin pathways in the brain
Distribution of acetylcholine receptors in the brain
Stress and anxiety affect
nicotine tolerance and
dependence. The stress
hormone corticosterone
reduces the effects of
nicotine; therefore, more
nicotine must be consumed
to achieve the same effect.
This increases tolerance to
nicotine and leads to
increased dependence.
Studies in animals have also
shown that stress can
directly cause relapse to
nicotine self-administration
after a period of abstinence.
In 1992, WHO for the first time, included tobacco smoke in the
chapter dedicated to "MENTAL and BEHAVIOURAL
DISORDERS caused by psychoactive substances."
Nicotine, which is responsible for nicotine addiction, may be
defined as a psycoactive substance whose action consists mainly
in the activation of cerebral centers:
1) The dopaminergic mesolimbic system is regarded as the
cerebral centre of pleasure and gratification, since the subject tries
to recover the exhilarative effect of the product (CRAVING).
The central nervous system
Reticular activating system
Basal ganglia
Limbic system
Cerebral cortex
Hypothalamus
The RAS is the attention center in the brain. It is the key
to "turning on your brain," and seems to be the center of
motivation. The RAS is connected at its base to the spinal
cord where it receives information projected directly from
the ascending sensory tracts. The brain stem reticular
formation runs all the way up to the mid brain. As a result,
the Reticular Activating System is a very complex
collection of neurons which serve as a point of
convergence for signals from the external world and from
interior environment.
 RAS is very susceptible to the effects of drugs:
LSD, cocaine, amphetamine, alcohol, barbiturates
BG are the primary centers for involuntary and finely tuned motor
functions, posture and muscle tone. Damage to BG may cause
Parkinson’s disease. Heavy use of tranquilizers for psychotic
patients can produce Parkinson-like syndromes.
Limbic system
It appears to contribute to the characteristics of the individual and the
continuation of human life. The limbic system is responsible for
feeding behavior, “fight and flight reactions”, aggression, the
formation of memories and the emotional life. The limbic system
receives input from many parts of the cerebral cortex and contains
association areas where various aspects of sensory experience come
together to form a single experience.
Self-administration of stimulant drugs (amphetamine & cocaine)
occurs in Limbic system.
Limbic system’s transmitters: dopamine, NE, & 5-HT.
The endocrine system
The endocrine system consists of glands
which release hormone into the bloodstream.
Regulation of metabolism, growth, tissue
repair, sexual behavior, etc.
Hormone has a slower onset, a longer
duration of action, and a more generalized
target.
The abuse of hormones
 Androgens: testosterone (natural androgen)
 Anabolic steroids:
 They are abused by many athletes & trainers
 Side effects: early heart disease, sudden death, the
increase of LDL, lower HDL, an increase in tendon injuries,
liver tumors, testicular atrophy, gynecomastia, male pattern
baldness, severe acne, premature closure of growth plates
in adolescents, emotional disturbances and other significant
health risks.
 Designer steroids: tetrahydrogestrinone (2003),
gastrinone, trenbolone
ANABOLIC STEROIDS:
THE ROAD TO THE GOLD
OR THE ROAD TO THE GRAVE