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WEBSITE DISCUSSION QUESTIONS AND IDEAS
1. Schwarting and Huston (1997) found rats with between
45-65% dopamine (DA) damage rotated ipsilaterally in response to apomorphine ( APO),
in contrast to most other studies which reported contraversive turning. One hypothesis
is that damage to non-DAergic neurons caused this unusual rotation; alternatively,
slight differences between rat brains could lead to dissimilar behavior. Can you
think of another reason the rats might rotate ipsilaterally after APO, based on
the mechanisms of APO in the brain?
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The ipsiversive turning may have resulted because the moderate lesion (45-65%) was
not severe enough to trigger the post-synaptic DA receptor supersensitivity that
usually causes contraversive turning. However, Schwarting and Huston note that there
are currently no data regarding changes in postsynaptic DA receptor sensitivity
for lesions of this magnitude (1997).
The authors hypothesize that the unusual turning behavior may be due to presynaptic
compensatory measures. The D2 autoreceptors regulate these mechanisms, which include
synthesizing, metabolizing, and releasing DA. If the autoreceptors’ sensitivity/function
changed after the lesion, the resulting presynaptic changes could lead to ipsiversive
turning behavior.
Schwarting, R.K. & Huston, J.P. (1997). "Behavioral and neurochemical dynamics
of neurotoxic meso-striatal dopamine lesions." Neurotoxicology,18, 689-708.
Schwarting, R.K.W. & Huston, J.P. (1996). "The unilateral 6-hydroxydopamine
lesion model in behavioral brain research. Analysis of functional deficits, recovery
and treatments." Prog Neurobiol., 50, 275-331.
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2. While most studies found that a massive amount of damage (>90% DA denervation)
was necessary to induce APO rotation, Schwarting and Huston (1997) reported rotation
even after 35% damage (similar results were reported by Fornaguera et al. in 1993).
How do you explain this finding?
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The graphs in this study measured turning behavior according to quarter turns, which
may have been misleading (many other studies use full turns). The slight differences
in ipsilateral versus contralateral turning could be due to chance, prior exposure
to APO, changes outside the neostriatum (i.e. in the ventral striatum), and compensatory
measures as a result of lesion damage.
Schwarting, R.K. & Huston, J.P. (1997). "Behavioral and neurochemical dynamics
of neurotoxic meso-striatal dopamine lesions." Neurotoxicology,18, 689-708.
Schwarting, R.K.W. & Huston, J.P. (1996). "The unilateral 6-hydroxydopamine
lesion model in behavioral brain research. Analysis of functional deficits, recovery
and treatments." Prog Neurobiol., 50, 275-331.
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3. There are several methods of measuring rotational behavior—many studies
use either a flat-surface or bowl-shaped rotometer (click here for picture). Ungerstedt
(1970) found that different methods led to slightly different rates of rotation,
although the differences were not statistically significant. How do you explain
this finding?
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Ungerstedt hypothesizes that the rats become distracted in a larger environment,
and thus rotate less.
Ungerstedt, U. & Arbuthnott, G.W. (1970). "Quantitative recording of rotational
behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine
system." Brain Res., 24, 485-493.
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4. Research shows that rats may become conditioned to the rotometer with time,
leading to “learned rotation.” Why might this be a problem? How could
this problem be alleviated?
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This is a problem because it can skew the data, leading a researcher to believe
that differences in turning behavior are a result of DAergic mechanisms, while they
actually reflect conditioning—an entirely different phenomenon. The problem
might be alleviated if several different methods for recording rotational behavior
were used, such as video analysis, a flat rotomoter, and curved rotomoter. Researchers
could be blind to which drug they were administering to the rat, so that prior expectations
would not influence the animal’s behavior. The drugs could even be randomly
administered, so that the rat might not receive the same drug each day and therefore
would not become conditioned to turning only in one direction.
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5. Based on the existing literature, do you think the lesion site affects rotational
behavior? If so, explain your reasoning.
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The lesion site determines the amount of DA denervation, which corresponds to the
subsequent rotational behavior. If the lesion site is outside of the SN or striatum,
the rat might not rotate.
Also, lesions outside the neostriatum can affect DAergic receptor function in various
ways, leading to changes in resultant turning behavior.
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