Last minute essential exam prep Flashcards
Why do people deliberately take drugs? (give anatomy based reason)
Because of the realese of (neurotransmitter) dopamine. Specifically, the mesolimbic dopamine pathway (ventral tegmental area [VTA - in the mid brain] and the Nucleus accumbens [NA] -part of the basal ganglia] and path up to the prefrontal lobes) (i.e., reward circuit)
What is addiction?
A state characterised by a compulsiuon to take drugs periodically or continuosuly in order to experience the rewarding effects and avoid the discomfort of its absence.
what is physical drug dependence (Drug abuse)?
when not taking the drug produces withdrawal symptoms.
- In heroin dependence those symptoms are sweating, goosebumps, diarrhoea, muscular spasms, aches and pains.
- In alcohol and benzodiazepine dependence those symptoms are hypersensitivity to sound and light, anxiety, convulsions, coma or occasionally death (if withdrawal is too abrupt).
what is psychological drug dependence (Drug abuse)?
is when you crave the drug during abstinence and causes a high level of relapse.
Research suggests that craving may be due to increased _______ release from the prefrontal cortex to the nucleus accumbens. This is the major excitatory neurotransmitter in the brain. The anterior cingulated cortex and the amygdale both signal the nucleus accumbens using it when addicts are shown relevant drug paraphernalia. It has also previously been shown to be important in learned associations.
Glutamate
What are the drug treatments for heroin and how do they work?
(Heroin acts to increase dopamine through the mu receptor mostly in the nucleus accumbens and ventral tegmental area which makes it basically a really good pain killer.)
- Methadone - binds to the mu receptor (mu receptor agonist) and binds for longer than heroin would, reducing the ability for heroic to bind. It has a slow mechanism and a small effect so you don’t get the rush like you would with heroin
- **Buprenorphine **- binds to the mu receptors but has less efficacy (a partial agonist) than methadone
- **Naloxone **- a mu receptor antagonist (competitive binding) that blocsk heroin activating mu receptors to release dopamine . often used in emergencies to treat an overdose, but compliance is a problem in drug abuse treatment.
- **Buprenorphine + Naloxone **- aimed at modifying how heroin gets to the mu receptor whilst trying to maintain compliance
how does heroin affect the user?
Heroin acts to increase dopamine through the mu receptor mostly in the nucleus accumbens and ventral tegmental area which makes it basically a really good pain killer.
What are the drug treatments for alcohol and how do they work?
- Acamprosate (Campral) is an NMDA (a type of Glutamate receptor) antagonist and reduces cravings.
- Naloxone blocks the effect of alcohol on mu receptors.
- Disulfiram (Antabuse) forces abstinence by making alcohol use very unpleasant. If you take alcohol with disulfiram you will be violently ill through a chemical gastrointestinal reaction. It is used to detoxify alcoholics.
How does alcohol affect the user?
Works on a lot of receptors. Works on GABA which is the main inhibitory neurotransmitter in the brain which is the main reason that alcohol males you feel sleepy.
What are the drug treatments for nicotine and how do they work?
- Nicotine Replacement therapies - Mostly designed to ween the additc of smoking as a way of stopping the harmful effects of cigarettes. It relives the psychological and physical symptoms of cravings.
- Buproprion is a dopamine reuptake inhibitor and an antidepressant. It is often used as an adjunct to NRT. The flood of dopamine in the synapse makes any more dopamine released by nicotine ineffective.
- Vareniclineis a nicotine receptor partial agonist, competing with nicotine for binding.
- Nicobrevin is weird and Jen is not sure how it works. Contains: camphor, eucalyptus oil, menthyl valerate, quinine.
what is colidine?
an agonist at alpha2 adrenoceptors (noradrenaline). It helps to reduce the withdrawal effects of opioids, cocaine and nicotine but it can make you dizzy
What are benzotropines?
(psychostimulant replacement therapy) is similar to methadone but aimed at blocking the dopamine transporter.
They are long acting and can prevent cocaine from having the same effect on the dopamine transporter. Cocaine works by blocking the dopamine transporter.
What is panic-agoraphobia syndrome?
Panic disorder
- Episodic in nature
- Experience shortness of breath
- Increases or irregularities in heart rate (sympathetic nervous system overload)
- Loss of control in a situation
- Extreme fear
- Anticipation of continued panic attacks may lead to Agoraphobia (fear of open or unfamiliar places) Continual fear of panic attacks in unfamiliar territory is Panic-Agoraphobia syndrome
What is the ANS response to phobia?
Increased sympathetic nervous system activity including:
- Skin - piloerection and sweating
- Pupils dialte
- Blood vessels - increased blood pressure
- Trachea/lungs - hyperventilation
- Heart - increased heart rate/tachycardia
- Stomach - stomach secreations
- Bowel - increased defaecation
- Bladder - increased urination
What neuranatomical structures and chemical brain systems are involved in panic disorder?
Neuroanatomy
- Amygdala - involved in emotional response
- Hippocampus - remembering/associating awful situations
HUGE ROLE IN ANXIETY ^
+
- Peri-aqueductul grey - involved in defense, an acute effect. fearful response
- Cigulate cortex an frontal cortex
Chemical:
- **All regions overstimulated by noradrenaline originating from the rostal raphe nuclei and caudal raphe nuclei **(in the brainstem)(inc. ANS) [primary neurotransmitter for SNS] (alpha 2 receptors) - responsible for state of arousal, tlles the prefrontal cortex to panic.
- to hippocampus
- to cortex
- to cerebellum
- to thalamus
- etc
-
LACK of Serotonin (which normally calms things down)
- in amygdala (emotion/fear)
- periaqueductal greey (Defensive behaviour)
- limbic cortex (influence over hypothalamus)
- Hypothalamus (important for intergrating autonomic, somatic responses and the released of hormones such as cortisol and adrenalin —emotional responses
What are phobias?
Intense irrational fear of ‘something’:
Particular situation
Specific object
Specific activity
Negative reinforcement strengthens avoidance
Symptoms of panic will occur if person is faced with phobia
e.g.,
- Arachnophobia: fear of spiders
- Claustrophobia: fear of closed spaces
- Taphephobia: fear of being buried alive
- Vestiophobia: fear of clothes
- Pentheraphobia: fear of mother-in-law!
What neuranatomical structures and chemical brain systems are involved in panic disorder?
Neuroanatomy
- Amygdala - involved in emotional response
- Hippocampus - remembering/associating awful situations
- Frontal lobe, parietal lobe, occipital lobe
- cerebellum
- Thalamus & hypothalamus
Chemical:
**All regions overstimulated by noradrenaline originating from the rostal raphe nuclei and caudal raphe nuclei **(in the brainstem)(inc. ANS) [primary neurotransmitter for SNS] (alpha 2 receptors) - responsible for state of arousal, tlles the prefrontal cortex to panic.
- to hippocampus
- to cortex
- to cerebellum
- to thalamus
- etc
LACK of Serotonin (which normally calms things down)
- in amygdala (emotion/fear)
- Cerebral cortex - less focused on information from the environment
- limbic cortex (emotion) - cortical influence over the hypothalamus
- Hypothalamus (memory) negative associations enhanced
All of the the anixety disorder share common effects on certain neurotransmitters and brain regions….these are?
- Amygdala (emotional response/fear)
- Hippocampus (memory and memory associations)
- Thalamus (relay center and affects alertness) and hypothalamus (regulates ANS e.g., tells piturity to release cortisol via ACTH and enables intergration of information from the environment)
- Dorsal OR Rostal Raphe Nuclei (in brainstem) produce serotonin
- Locus Coereleus (in pons) - stress and panic
- REDUCED serotonin (calming)
- INCREASED noradrenaline (increased ANS activity, acts on alpha 2 receptors)
The defining neuroanatomy differences of Panic disorder are? (in addition to the basic systems affected by anxiety disorders)
- Periaqueductal grey (defence/fear response)
- Cigulate and frontal cortex (increased noradrenaline and decreased serotonin tells these areas to ‘panic’)
- particularly strong stress reaction of the ANS (SNS) via the hypothalamus telling the adrenals to reduce cortisol
The defining neuroanatomy differences of Phobias are? (in addition to the basic systems affected by anxiety disorders)
- Particularly strong hippocampal involvement - learned associations with fearfull stimuli
- Limbic cortex/hypothalamus - strong release of cortisol/stress reponse to the fearfull stituation
- Cerebral cortex- becomes less focused on the environment
The defining neuroanatomy differences of Generalised Anxiety Disorder are? (in addition to the basic systems affected by anxiety disorders)
The following systems received extra noradrenaline and insufficient serotonin
- Involvement of the basal ganglia - difficulty processing information from the environment
- Cerebral cortex (prefrontal) - inabilityt o adequately execute appropriate responses to information from environment
- Limbic cortex/amygdala - emotion and control of hypothalamus.
The defining neuroanatomy differences of OCD are? (in addition to the basic systems affected by anxiety disorders)
May be caused by uncontrolled communication (loop) between
frontal, striatal and thalamic structures? Insel 1992 (Lesions of frontal (cingulate) cortex neurons (cingulotomy) breaks the loop and helps OCD patients)
- basal ganglia and Substantial nigra involvment – learning of repetitive behaviours via the dopamine reward circuit
- Less noradrenaline effect - less cerebellar and sympathetic outflow than other disorders
*
The defining neuroanatomy differences of OCD are? (in addition to the basic systems affected by anxiety disorders)
Amygdala becomes dominant, hippocampus shrinks- the amygdala says “don’t listen to the hippocampus “(which could provide helpful memories to overcome fear!) - leads to
exacerbation of negative emotion linked to the memory of event.
Amygdala dominates over hippocampus in communicating with the hypothalamus (Which regulatees ANS) THEREFORE, hypothalamus signals pituritary glad with ACTH to secrete more cortisol into the blood. (Cortisol then tells hippocampus to tell the amygdala to reduce the requests for cortisol! but amygdala is TOO STRONG!!)
How can the hyperactivity of neural circuits be reduced (to treat anxiety)?
- Increase negative charge into the neuron (chloride ions Cl-) i.e., enhance inhibitory neurotransmission (IPSP - inhibitory postsynaptic potential)
- Enhance GABA receptor activation to enhance Cl (chief inhibitory neurotransmitter in the CNS)
What were the early treatments for Anxiety? (why and why are they not used often now?)
Early treatments consisted of using barbiturates
• Act as GABA Receptor agonists - not very selective
- High incidence of side effects (sedation, fatal overdose)
- Highly addictive
- Best used as anaesthetics
What type of drug is typically used to treat anxiety disorders now? (how does it work?)
benzodiazepines (benzos) (1970-80’s)
• More selective as GABA receptor agonists
Benzodiazepines enhance the effect of GABA on it’s
receptor
- Benzodiazepines have their own binding site on the GABA receptor: Bz1 and Bz2
- The GABA-A receptor can bind both GABA and Benzodiazepines to enhance receptor function on the dendrite of the neuron
- i.e., Keep the ion channel open for longer- binding the benzodiazepines keeps the ion channel open for longer so more Chloride ions (CL-) can get in, having an inhibitory effect on the neuron.
What is GABA?
the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays the principal role in reducing neuronal excitability throughout the nervous system.
What is a benzodiazepine? (how does it work?
Benzodiazepines have their own binding site on the GABA receptor: Bz1 and Bz2
The GABA-A receptor can bind both GABA and Benzodiazepines to enhance receptor function on the dendrite of the neuron
i.e., Keep the ion channel open for longer- binding the benzodiazepines keeps the ion channel open for longer so more Chloride ions (CL-) can get in, having an inhibitory effect on the neuron.
(1)______________ are a GABA receptor agonist - they enhance the effect of GABA on its receptor
they have their own binding site on the GABA receptor: Bz1 and Bz2
The GABA-A receptor can bind both GABA and (1) __________ to enhance receptor function on the dendrite of the neuron
i.e., Keep the ion channel open for longer- binding the (1)____________ keeps the ion channel open for longer so more Chloride ions (CL-) can get in, having an inhibitory effect on the neuron.
Benzodiazepines
What early treatment of anxiety
- acts as a GABA receptor agonist (not very selective)
- Had high incidence of side effects (Sedation, fatal overdose)
- Highly addiction
- Best used in anaesthetics
Barbiturates
How does a barbituate work, why is it not a great anxiety treatment?
Acts as a GABA receptor agonist (not very selective)
Had high incidence of side effects (Sedation, fatal overdose)
Highly addiction
Best used in anaesthetics
What drug is an agonist at alpha2 adrenoceptors (noradrenaline). It helps to reduce the withdrawal effects of opioids, cocaine and nicotine but it can make you dizzy
Colidine
