Neurobehavioral Plasticity: Learning, Development, and Response to Brain Insults

By Norman E. Spear; Linda P. Spear et al. | Go to book overview
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TABLE 17.4
Summary of EEDQ's Effects on Various Presynaptic Measures in 17-Day-Old and Adult Rats
D1/D2 Receptor
17-Day-Olds90-Day-OldsMediated
DA levelsDecreasedDecreasedNo
DOPAC levelaNo effectIncreasedNo
DOPAC effluxbNo effectIncreasedNo
(after pargyline)
DA accumulationbNo effectNo effect---
(after pargyhne)
DOPA accumulationcIncreasedIncreasedYes
(after NSD-1015)
a A measure of the combined effects of DA synthesis and catabolism
b An estimate of DA turnover.
c An estimate of DA synthesis.

and adult rats; however, pretreatment with reversible antagonists was only able to protect the amphetamine-induced behaviors of the older animals.

These results leave us with an interesting possibility: that EEDQ disrupts the NPA- and amphetamine-induced behaviors of adult rats by inactivating postsynaptic DA receptors, but that EEDQ disrupts the amphetamineinduced behaviors of preweanling rat pups by reducing DA levels. In adult rats, EEDQ's actions are apparently receptor mediated, because EEDQ blocks the effects of both the direct receptor agonist NPA and the indirect agonist amphetamine. In the rat pups, behavioral deficits are only observed when DA levels are diminished by EEDQ and no direct receptor agonist is given (i.e., when amphetamine and not NPA or quinpirole is given). Thus, the amphetamine-induced release of DA is apparently insufficient to activate behavior. Again, EEDQ's receptor-depleting effects do not seem important for preweanling rats, because pretreatment with SCH 23390 and sulpiride was unable to protect the amphetamine-induced behaviors of the 17-day-old rats. Therefore, although a precise explanation for EEDQs' ontogenetic effects is not yet available, we believe that fully understanding these age-dependent differences will provide important knowledge for understanding the relationship between DA receptors and behavior.


REFERENCES

Adler C. H., Meller E., & Goldstein M., ( 1985). "Recovery of cc-adrenoceptor binding and function after irreversible inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)". European Journal of Pharmacology, 116, 175-178.

Arnt J., Hyttel J., & Meier E. ( 1988). "Inactivation of dopamine D-1 or D-2 receptors differentially inhibits stereotypies induced by dopamine agonists in rats". European Journal of Pharmacology, 155, 37-47.

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