NSC 243: Practice Exam I
(1995)

1. From the following experimental evidence, you are to determine the anatomic interactions that exist between the cholinergic, dopaminergic and GABAergic neurons.

  1. Systemic injection of picrotoxin(a GABA receptor blocking agent) increased ACh in the caudate nucleus by 70%. What would be the effect at a given GABA synapse of blocking the GABA receptor?
  2. Systemic injection of picrotoxin increased homovanillic acid ( metabolite of dopamine) in the caudate nucleus by 30%. Where is the origin of DA terminals in the caudate nucleus?
  3. Adding picrotoxin in vitro slices from the caudate nucleus did not change choline acetyltransferase activitiy. What is choline acetyltransferase a measure of and what does this information tell you about the locus of action of picrotoxin in steps A and B?
  4. The effect of systemic picrotxin on ACh levels in the caudate nucleus was completely blocked by pretreatment of the animal with an inhibitor of tyrosine hydroxylase. Which transmitter system in question is this enzyme related to and how?
  5. NOW: Diagram the most probable anatomical relationship between the cholinergic, dopaminergic and GABA ergic neurons. Be sure to clearly label the region of origin and of termination of a given transmitter-containing neuron.
2. Amino acids have been proposed as the neurotransmitter in hair cells in the cochlea. In the following study, the efflux of several amino acids from superfused hair cell sheets was examined. In the control condidition, the preparation was perfused with physiological saline containing 1.8mM Ca++ and 0.05mM Mg++. In the Magnesium condition, the preparation was perfused with saline containing 0mM Ca++ and 10.05mM Mg++. The cells were depolarized by the addition of K+, at 14mM during both perfusion conditions. The data are presented as the depolarized efflux minus the baseline efflux(no K+).

Changes in efflux of amino acids with elevated K+
Compound             Control        Magnesium

Glutamate            10.09            -2.5
Asparate              0.34            -0.59
Taurine              -4.2            -11.1
b-Alanine            -0.39            -0.77
Glycine              -0.67            -1.1
Glutamine            -1.7             -1.9
3. The effect of morphine on serotonin(5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) was investigated using microdialysis in the diencephalon. The extracellular levels of 5-HT and 5-HIAA are expressed as % baseline control.

  1. Morphine(20mg/kg) was injected systematically alone or in the presence of a monoamine oxidase inhibitor(MAO I) or a 5-HT uptake inhibitor(UI). The following date were obtained:

    Extracellular Levels (% baseline control)
                          5-HT               5-HIAA

Systemic morphine   130+/-8             180+/-12
Systemic saline     100+/-5             100+/-12
Morphine + MAO I    160+/-7             Not detectable
Morphine + UI       160+/-6             130+/-4
  2. Systemic morphine clearly increased the extracellular levels of 5-HT and 5-HIAA. What effects did the MAO and 5-HT uptake inhibitors have on the measured responses to morphine? Explain why those compunds elicited those effects? Be thorough in your answer; consider the effects on both 5-HT and 5-HIAA.

  3. The effect of the systemic injection of morphine was compared to the effect of direct infusion of morphine into the area of 5-HT terminals in the diencephalon or of microinjection of morphine into mesencephalic raphae nuclei. The effect of the opioid receptor antagonist, naltrexone, was also evaluated. The following data were collected:

    extracellular levels (% baseline)
                             5-HT                5-HIAA

systemic morphine       130+/-8             180+/-12
systemic morphine
  +naltrexone           100+/-4             100+/-6
morphine infusion
  into diencephalon     100+/-8             100+/-5
morphine injection   
  into raphae nuclei    130+/-12            165+/-4
morphine injection
  into raphae 
  + naltrexone          100+/-3             110+/-6
  4. At what anatomical aspect of 5-HT neurons is systemically injected morphine most likely exerting an effect? explain.

6. The effect of single (acute) or multiple (chronic) injections of haloperidol (a dopamine reeptor antagonist) or saline on the Km of tyrosine hydroxylase for its cofactor, tetrahydropterin are presented below. Chronic injections were given once daily for 14days. Tyrosine hydroxylase activitiy was determined at one an 24 hrs after the 14th or the single injection.

Km of Tyrosine Hydroxylase for its cofactor
                 Acute                       Chronic
Time       Saline     Haloperidol      Saline   Haloperidol

1  hr.      0.92         0.23           0.59       0.27
24 hrs.     0.96         0.93           0.62       1.70
  1. Compared to the relevant control group (saline), did the effect of haloperidol vary between acute and chronic-exposed animals at one hour after injection? Does any change induced by the drug reflect an increased or decreased sensitivity to the cofactor. Quantify your answer.
  2. Is the sensistivity of the enzyme for the cofactor different at 24 hrs after injection than at one hour? How did any change from one to 24 hours differ between the acute and chronic condition. Explain and support your answer with data.

9. The following figures illustrate tyrosine hydroxylase (TH) activity (pmol/mg tissue/hr) and TH mRNA levels in the adrenal medulla of young adult (5 month) and aged (25 month) rats under control conditions and following 10 weeks of training on a treadmill (trained). After training, maximum oxygen consumption increaed by 20% at both ages. However, in both condidtions, maximum oxygen consumption was significantly less in the aged rats.

  1. What is the effect of ageing on TH activitiy in the adrenal medulla of control rats? Is the effect most likely related to a change in kinetic action of the enzyme or increased production of the enzyme? Explain.
  2. What efefct does 10 weeks of treadmill running have on TH activitiy in the young adult rat (5 month) and is the effect reflective of altered enzyme activation or a change in the amount of enzyme? Explain. From the information given, what factor(s) might have been responsible for the training-induced change in enzyme activity.
September 20, 1995