Which three neurotransmitter systems have been implicated in anxiety?

GABA- benzodiazepine receptor complex-

NE system (locus coeruleus), Seretonin (Raphe Nucleus)

Describe the synthesis of GABA. How is it cleared from the synapse?

Describe the GABA A receptor. What is the role of the benzodiazepine receptor in neuronal firing?

There are two subtypes of GABA receptors - GABA A and GABA B

GABA A receptor are gatekeepers for a chloride channel.

It has 3 subunits - alpha, beta, and gamma

The combination of an alpha and beta subunit of GABA A receptor is enough to creare a binding site for GABA.

It is allosterically modulated by benzodiazepine receptor and configures two or more NT receptor sites so that one can boost or blunt the activities of the other. Located on same or neighboring receptors. Benzodiazepine joins alpha and beta parts to create a binding site for benzodiapines. Together they modulate a chloride channel, and an influx of chloride ions is inhibitory to neuronal firing.

What is allosteric modulation? What is an inverse agonist?

it is when two or more NT receptor sites are configured so that one can boost or blunt the activities of the other. It may be located on the same or neighboring receptors. Usually only primary receptor site turns on second messenger or alters ion channel. But it may require the second NT binding at a secondary site. This indirect influence is allosteric modulation.

The most important thing to get is that molecules and bits of molecules cooperate to control neurotransmission at this ligand-gated channel.

An inverse agonist does the opposite of an agonist by binding to the neurotransmitter receptor in a way that it causes an action opposite to that of an agonist.

What is the result of electrical stimulation of the locus coeruleus? What is buspirone and its effect on anxiety?

The result is tachycardia, tremor, and sweating. Buspirone is a serotonin 1A partial agonist that has been show to mediate anxiety in some animal models and GAD

Briefly compare/contrast barbiturates and benzodiazepines

Barbiturates were early drug treatments. They were more acting like sedatives which reduced anxiety in direct proportion to their ability to sedate; just masked anxiety. Led to dependence, withdrawal problems, and high risk of overdose.

Benzodiapines

Selective anti-anxiety effects were observed, although some are more sedating than others

anticonvulsant and muscle relaxant properties

much safer than barbiturates

Can provide rapid relief with little risk of dependence or withdrawal if use is limited to several weeks to a few months

Name 5 anxiety disorder subtypes that fragmented from GAD

What is the clinical description of OCD

characterized by obessions and/or compulsions that together last at least an hour a day and interfere with one's normal social or occupational functioning.

Obsessions-- experienced internally and subjectively by the patient as thoughts, impulses or images. Intrusive, inappropriate, and cause marked anxiety and distress.

Compulsions--Repetitive behaviors or purposeful mental acts. Can sometimes be observed by others. Often performed in response to an obsession or according to rigid rules aimed at preventing distress or negative event

Briefly, what are the three biological hypotheses of OCD?

What are four combination drug therapies for OCD?

1. replete serotonin if it's not there. Slow serotonin neuronal firing with a 5HTIA a partial agonist- buspirone.

serotonin stores can build up due to continued synthesis

2. Perhaps a neuron is incapable of releasing its serotonin, so we want to increase that by using Fenfluramine. We can block its reuptake.

3. Add a neuroleptic that blocks DA receptors such as good for those with TS, associated schizophreniform- type symptoms, or delusions.

4. add a beonzodiazepine which allows for a higher dosage of SSRIs to be tolerated, partially by reducing anxiety-related symptoms.

What is the difference between a panic attack and a panic disorder? What may be neurotransmitter dysfunction leading to panic disorder?

panic attack is a discrete episode of unexpected terror accompanied by a variety of physical symptoms

catastrophic thinking, sense of impending doom, belief that loss of control, death or insanity is imminent. neurological, gastrointestinal, cardiac, pulmonary symptoms. Duration is 5 to 30 minutes, but can last hours. May occur during sleep

Panic disorder is the presence of recurrent unexpected panic attacks followed by at least 1 month period of persistent anxiety or concern about the attacks.

Neurotrasmitter dysfunctions include excess of NE, leading to down-regulation of post-synaptic adregernic receptors.

GABA dysfunction an abnormality in the benzodiazepine receptor is suggested by studies, chloride channel conductance is low, and patients require administration of exogenous benzodiazepines to ''reset'' the receptor complex to normal.

What is the false alarm theory of panic disorder? What is Ondine's curse?

a suffocation monitor located in the brainstem misinterprets signal and misfires, triggering a ''false'' suffocation alarm'' (inhaler story)

Ondine's curse (congenital central hypoventilation syndrome) is opposite, with a diminished sensitivity of suffocation alarm; lack of adequate breathing.

List describe the four da PATHWAYS ON THE HANDOUT

The Nigrostriatal system which extends from the substantia nigra to the caudate nucleus putament neostriatum) and is concerned with sensory stimuli and movement.

The mesolimbic system which extends from the ventral tegmentum of the midbrain to the limbic areas and is thought to be associated with cognitive reward and emotional behavior.

The mesocortical system which extends from the ventral of the midbrain to the cortex (forebrain) and has to do with higher cognitive functions

The tubero-infundibular system between the hypothalamus and pituitary gland and is concerned with neuronal control of the hypothalmic-pituatory endocrine system

Sometimes the mesolimbic and mesocortical systems are combined into one but they really have different functions

What are delusions? Hallucinations? What is the difference between positive and negative symptoms of Schizophrenia?

Delusions -- erroneous beliefs involving misinterpretation of perceptions or experience

Hallucinations -- may occur in any sensory modality, but auditory hallucinations are the most common. Experience of perception that is not present.

Positive symptoms are an excess of normal functions, behaviors that are present but should be absent

Negative are diminished or lack of behavior.

What are some of the neuroanatomical abnormalities in schizophrenia patients?

Ventricles are on average 40 % larger.

Reduced brain volume-- number of neurons is normal, but they are deeper and packed more tightly than they should be

Smaller cerebral cortex, less gray matter, smaller temporal lobes, smaller limbic region, loss of neurons in the thalamus and cerebellum, asymmetry. Mystery particle

What is the P300 response? What is the difference in this response in schizophrenia patients compared to normals?

It is a positive electrical spike that occurs about 3/10 of a second after a stimulus that is unexpected or relevant for action. This is even before the stimulus is consciously recognized.

Schizo shows that response is delayed and weak.

What is thought to be the primary biological basis of the positive symptoms of schizophrenia?

What is a neuroleptic? How does it affect da? How do atypical antipsychotics differ from the conventional neuroleptics?

A term that refers to the effects of antipsychotic drugs on a patient, especially on his or her cognition and behavior.

Neuroleptic drugs may produce a state of apathy, lack of initiative and limited range of emotion. In psychotic patients, neuroleptic drugs cause a reduction in confusion and agitation and tend to normalize psychomotor activity.

blocks postsynaptic DA receptors specifically in this pathway diminishes positive symptoms. Most block D2 receptors.

Atypical antipsychotics don't block DA in all four systems and only block selectively in the mesolimbic receptors.

has atypical properties; more effective than typical neuroleptics in some patients, one of most complicated drugs in psychopharmacology and it has notable interactions with at least nine neurotransmitter receptors.

Can cause a potentially fatal bone marrow toxicity known as agranulocytosis.

What are EPRs? What is tardive dyskenisia?

Extrapyramidal reactions are drug induced parkinsonism due to blockade of receptors in the basal ganglia.

Tardive dyskinesia is slow faulty movement. facial tics and gestures such as lip-smacking, tongue protrusions and other hyperkinetic movemments.

Results from a long-term blockade of nigrostriatal DA receptors by neuroleptics - postsynaptic receptors upregulate to try to compensate for low DA levels. Can be irreversible.

What are potential effects of blocking DA receptors in the mesocortical DA system? What is neuroleptic-induced deficit syndrome? In the tuberoinfundibular system?

DA pathways is involved with negative as well as positive symptoms, and blocking DA activity here will reduce negative symptoms vs. conventional neuroleptics are not useful and may even produce more negative symptoms themselves (coginitive side effects of neuroleptics = neuroleptic- induced deficit syndrome)

Blocking DA in the tuberoinfundibular pathway lead to an increase in prolactin levels and inapproriate lactation in women.