Neurotransmitters – Functions & Mechanism Of Action In Cns

NEUROTRANSMITTERS – FUNCTIONS & MECHANISM OF ACTION IN CNS

Q. 1

5-HIAA (Hydroxyindoleacetic Acid) is a metabilite of which of the following neurotransmitters?

 A

Noradrenaline

 B

Serotonin

 C

GABA

 D

Glutamine

Q. 1

5-HIAA (Hydroxyindoleacetic Acid) is a metabilite of which of the following neurotransmitters?

 A

Noradrenaline

 B

Serotonin

 C

GABA

 D

Glutamine

Ans. B

Explanation:

Serotonin (5-HT) is metabilised the key enzyme Mono Amino Oxidase (MAO) and one of the main metabolite of clinical significance is 5-HIAA.

The CSF levels of 5-HIAA (Hydroxyindoleacetic Acid) is low in patients who committed suicide, in depression and violence.

It is considered to be associated with poor impulse control. It can be used to predict violent suicide. It is not known to be reduced in OCD.

Ref: Kaplan & Sadock’s Synopsis of Psychiatry, By Benjamin J Sadock, M.D., Harold I. Kaplan, Virginia A Sadock, M.D, 10th Edition, Page : 265

Q. 2

Which of the following neurotransmitters are implicated in both mania and depression?

 A

GABA & dopamine

 B

Serotonin and Nor epinephrine

 C

Serotonin and dopamine

 D

Nor epinephrine and GABA

Q. 2

Which of the following neurotransmitters are implicated in both mania and depression?

 A

GABA & dopamine

 B

Serotonin and Nor epinephrine

 C

Serotonin and dopamine

 D

Nor epinephrine and GABA

Ans. B

Explanation:

Increase of Norepinephrine (noradrenaline) and serotonine levels causes mania and reverse cause depression.

Hence, the treatment of depression involves increasing serotonin levels and noradrenaline levels.

Antidepressants could trigger mania or hypomania due to excessive increase in the neurotransmitters in prone individuals.

Mania or hypomania induced by anti-depressants is called Bipolar III.


Q. 3

All of the following neurotransmitters are excitatory and inhibitory in function, EXCEPT:

 A

Glycine

 B

Glutamine

 C

Aspartate

 D

NO

Q. 3

All of the following neurotransmitters are excitatory and inhibitory in function, EXCEPT:

 A

Glycine

 B

Glutamine

 C

Aspartate

 D

NO

Ans. A

Explanation:

Glycine has both excitatory and inhibitory effects in the CNS.

When it binds to NMDA receptors, it makes them more sensitive to the actions of glutamate.

It is also responsible in part for direct inhibition, primarily in the brainstem and spinal cord.

Like GABA, it acts by increasing Cl- conductance. Its action is antagonized by strychnine.
 
Glutamate and aspartate are found in very high concentrations in brain, and both amino acids have powerful excitatory effects on neurons in virtually every region of the CNS.

NO acts as a signal by which postsynaptic neurons communicate with presynaptic endings to enhance release of glutamate.
 
Ref: Barrett K.E., Barman S.M., Boitano S., Brooks H.L. (2012). Chapter 7. Neurotransmitters & Neuromodulators. In K.E. Barrett, S.M. Barman, S. Boitano, H.L. Brooks (Eds), Ganong’s Review of Medical Physiology, 24e.  

 


Q. 4

Panic attack is associated with a disturbance in all of the following neurotransmitters except:

 A

Serotonin

 B

GABA

 C

Glutamate

 D

Dopamine, CCK, pentagastrin

Q. 4

Panic attack is associated with a disturbance in all of the following neurotransmitters except:

 A

Serotonin

 B

GABA

 C

Glutamate

 D

Dopamine, CCK, pentagastrin

Ans. C

Explanation:

C i.e. Glutamate

Panic disorder is associated with noradrenaline (norepinephrine), cholecystokinin (CCK)- pentagastrin /tetrapeptide (administration or agonism of both); GABA (antagonism) and serotonin (decrease). Glutamate studies are either equivocal or in preclinical phase d/t fear of convulsions.

Neurochemical Aspects of Panic Disorder

Panicogenic Agents

Intravenous sodium lactate or inhalation of 5-35% CO2 can induce panic attacks in perons with panic disorder while sparing those without such a history – these substances are k/a panicogenic. Other examples of panicogenic agents include caffeine, cholecystokinin 4, noradrenergic agents yohimbine & isoproterenol, CABA antagonist such as flumezanil, reverse benzodiazepine agonists such as /3-carbolines (because benzodiazepine agonists eg alprazolam, clonazepam treat panic disorders, so drugs reversing their actions precipitate panic attack).

Serotonin

Gorman’s neuroanatomical hypothesis states that both panic attack in humans & conditioned fear responses in animals are similar in autonomic arousal, fear evoked by specific cues (i.e. contextual fear) and avoidance of these cues. Both are mediated by fear network consisting of amygdala & its afferent & efferent projections particulary its connections with hippocampus, medial prefrontal

y-Amino Butyric Acid

GABA system is certainly involved in panic disorder as evidenced by

1)     Benzodiazepine agonist such as alprazolam, & clonazepam are effective in treatment of panic disorder.

2)     Reverse benzodiazepine agonist such as fl-carbolines cause panic attacks.

3)     CABA antagonist such as flumezanil have increased panicogenic effects.

Cholecystokinin (CCK)

Cholecystokinin (CCK) is a neuropeptide derived from 112 amino acid precursor compound which acts via CCK-A (CCK-1) and CCK-B (CCK-2) receptors. CCK-8 (octapeptide) is most abundant, does not cross BBB (so induce anxiety only after intracranial administration) and acts on both receptors CCK4 (tetrapeptide) is anxiogenic and a primary agonist of CCK-B receptors. Both CCK-4 and CCK-5 (pentagastrin) are panicogenic and effects could be blocked by CCK antagonist or treatment with GABA agonist such as vigabatrin or 

cortex, hypothalamus & brain stem. SSRIs desensitize the fear network. SSRIs increase serotonergic transmission in brain. Serotonergic neurons originate in brain stern raphe & project throughout CNS and some of these projections have inhibitory influences. For example the greater the activity in the raphe.

1) The greater the inhibition of noradrenergic neuron in locus cerulus (resulting in reduction in CVS sysmptoms such as tachycardia).

2) Greater the inhibition in periaqueductal gray region (resulting in reduction in avoidance behavior).

3)            Increased senetonergic activity also reduces hypothalmic release of corticotropin releasing factor, thereby resulting in a reduction of cortisol and reduction in activity of locus ceruleus thereby 1/t reduction in fear.

4) SSRIs may also directly inhibit activity of lateral nucleus of amygodala.

Noradrenaline

Noradrenaline (norepinephrine) agents yohimbine & isoproterenol stimulate panic attacks suggesting a possible subsensitivity of presynaptic a2 inhibitory adrenoreceptors. Both increase firing rate of locus ceruleus (brain alarm system). Most effective medications in treatment of panic disorder in fact decrease locus ceruleus firing rate & most panicogenic stimuli increase the locus ceruleus firing rate.


tiagabine. However, clinical trials of C1-988, a CCK-B antagonist have failed to abate (treat) anxiety symptoms induced by CCK-4 or MCPP.

Patients with panic disorder have lower CSF levels of CCK than healthy controls, although it is unclear whether it is d/t higher CCK turnover or greater receptor sensitivity.

CCK has its highest levels in the cerebral cortex, hippocampus, amygdala, caudate & putamen, with intermediate levels in thalamus & hypothalamus. It is also prevent in gastrointestinal tract. CCK receptors are found in greatest density in the cortex, hypothalamus, substantia nigra & PAG.

Glutamate

Glutamate is the primary excitatory neurotransmitter of CNS & precursor of GABA. It consists of 2 families of receptors: Metabotropic (m G1uR) & ionotropic receptors. Several preclinical (animal) studies have shown anxiolytic properties of group 2 & group 3 m-Glu- receptor agonist. However, human studies have failed to give a result distinct from placebo or were discontinued d/t findings of convulsions in animal studies of compound. This is understandable risk, given that glutamate enhancing drugs have neuro excitatory properties and glutamate inhibitors are used as anti convulsants. Similarly MG1u-5 and m GIuR7 antagonists and AMPA/kainate receptor blockers have shown antianxiety properties in animals.



Q. 5

Excitatory Neurotransmitters are :

 A

Acetyl choline

 B

Glycine

 C

GABA

 D

Glutamine

Q. 5

Excitatory Neurotransmitters are :

 A

Acetyl choline

 B

Glycine

 C

GABA

 D

Glutamine

Ans. D

Explanation:

D i.e. Glutamate



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