Flashcards in Case 8 Deck (39):
What is Dopamine?
hormone and neurotranmistter involved in motivation, reward and reinforcment. It is formed by removing a carboxyl group from L-DOPA by DOPA decarboxylase.
How is Dopamine action terminated?
In the synaptic cleft by reuptake of dopamine into nerve terminales and surrounding glial cells by sodium ion-dependent dopamine transporter.
What receptor type does dopamine work on?
G-protein coupled receptor
What are the two groups of dopamine receptors?
D1-type (D1 and D5 receptors) D2-type receptors (D2-D4).
How do D1 receptors function?
Receptors are coupled to the G protein GSalpha, this activates adenylyl cyclase, increasing extracellular cAMP.
How do D2 receptors function?
Coupled with the G protien GI alpha, which inhibits cAMP formation by inhibiting adenyly cyclase.
Where does the nigrostriatal pathway go from and to?
From the substantia nigra pars compacta (SNc) to the striatum.
What is the function of the striatum?
Dorsal striatum is involved in involuntary motor control and associative striatum is involved in learning, habituation, memory, attention, motivation, emotion and volition.
What is the order of the nigrostriatal pathway?
Medium spiny neurons of the corpus stiatum project into the SNc, which sends dopaminergic signals back to the spiny neurones. These pass through the direct or indirect pathway and have an antagonistic effect on the basal ganglia. This decreases the inhibitory outflow causing an increase in the excitability of upper motor neurones.
What is the direct pathway of the nigrostriatal pathway?
Excitory inputs from D1 type dopaminergic receptors on spiny cells that project into the internal globus pallidus.
What is the indirect pathway of the nigrostriatal pathway?
Inhibitory inputs mediated by D2 type dopaminergic receptors on the spiny cells that project into the external globus pallidus.
What is the mesolimbic pathway?
Goes from ventral tegmental area to limbic regions (including the nucleus accumbens in the ventral striatum, amygdala, hippocampus and the medial prefrontal cortex). These regions are associated with reward, motivation affect and memory and so play a major role in addiction.
What is the mesocortical pathway?
Goes from the Ventral Tegemental Area to the frontal cortex, this pathway is involved in cognative function, motivation and emotional response.
What is the tuberoinfundibular pathway?
Goes from the tuberal region to median eminence, dopamine acts to inhibit prolactin release from pituitary.
What are the three funtional pathways of the stiatum?
Sensorimotor - dopamine input from SNc, conatins D1 and D2 receptors. Associative - strong input from dorsolateral prefrontal cortex (DLPFC) and dopamine input from SNc, D1, D2 and D3 receptors. Limbic - Reward, dopamine input from VTA Contains D1, D2 and D3 receptors.
What is the prevalence of schizophrenia?
What is the epidemiology
slightly more common in women, more common in lower socioeconomic classes, Africa-Caribbean.
What are some alterations in brain structure thought to be implicit in schizophrenia?
enlarged cerebral ventricles, thinning of the cortex, decreased size of anterior hippocampus.
What factors can play a role in the development of schizophrenia?
Genetic, Environmental (stress or being born in winter months), Neurodevelpmental vulnerability, substance abuse (heavy cannabis use double risk, frquent use during teens can increase risk by 6 times).
What are the three catagories for symptoms of schizophrenia?
Positive, negative and cognative
What are positive symptoms?
Delusions, hallucinations and thought disorders.
What are negative symptoms?
Flat or blunter affect and emotion, alogia, inability to experience pleasure, lack of desire to form relationships, lack of motivation.
What are cognitive impairments?
Reduced attemtion, processing speed, working memory, abstract thinking, problem solving
What is the course of schizophrenia?
Wide variation. Usually follows a relapsing and remitting course. Patients may suffer one episode and return to normal or several episodes during which the illness never fully abates.
What is the dopamine hypothesis?
Psychotic episodes are triggered by activation of dopamine receptors. Increased activity in the mesolimbic pathway may cause positive symptoms, decrease of activity in the mesocortical pathway can cause negative symptoms.
What two observation support the dopamine hypothesis?
Effect of amphetamines in healthy people and neuroleptic drugs are potent blockers of D2 receptors.
What is the revised version of the dopamine hypothesis?
Not due to the mesolimbic pathway but due to increased dopamine presynaptic function in the nigrostriatal pathway. There is a small elevation of D2/D3 receptors.
What are the ionotropic glutamate receptors?
Ligand - gated ion channels divided into 3 main types NMDA, AMPA and the kainate type.
What ions is the AMPA receptor mainly associated with?
Na+ and K+
Describe the NMDA receptor in more detail?
Significantly associated with Ca2+ as well as Na and K ions. Under resting membrane potential conditions these receptors are blocked by Mg+ so it is only after the neural membrane depolarises and glutamate binds that the ion channels open. Glycine is also required as a co-agonist.
What is the glutamate hypothesis?
Diminished activation of NMDA receptors in the brain.
What are the 5 classifications of schizophrenia?
Paranoid, disorganized, catatonic, undifferentiated and residual.
How is schizophrenia diagnosed?
Assesment of history, symptoms and signs and information gained from collateral sources.
What is the treatment for schizophrenia?
Antipsychotics, rehabilitation, psychotherapy, family therapy, CBT.
What are the two classes of antipsychotics?
Conventional and 2nd generation
What is a common problem in schizophrenia?
Patients only partially complying
What is the mental health act of 1983?
An act covering the reception, care and treatment of mentally disordered patients, the managment of their property and other related matters. In particular it allows people to be detained in hospital or police custody against their wishes.
What is section 2 of the mental health act?
A patient can be detained for 28 days if: 1) they are suffering from mental disorder which warrants detention for assessment 2) They ought to be detained in the intrests of thier own or other peoples safety. It requiresthe written recommendations of two registered medical practitioners.