Summary
Lu 19-005 is a new phenylindan derivative with strong and equipotent inhibitory effect on dopamine (DA), noradrenaline (NA) and serotonin (5-HT) uptake. The adaptive effects of 2 weeks treatment with Lu 19-005, on receptor bindingin vitro and on d-amphetamine responsivenessin vivo have been investigated in rats. One or 3 days after the final dose the number ofβ-adrenoceptors and of 5-HT2 and DA D-2 receptors was decreased by 20–30%, whereasα 1-adrenoceptor number was slightly decreased only 1 day after withdrawal. The DA D-2 receptor number remained decreased at 7 days withdrawal, but returned to normal after another 3 days. The brain levels of DA, NA and 5-HT were not changed by 2 weeks' Lu 19-005 treatment. The down-regulation of DA D-2 receptors was accompanied by tolerance to d-amphetamine-induced hypermotility (after low doses) and stereotyped licking or biting (after a high dose). The tolerance to d-amphetamineinduced hypermotility was maximal at 3–5 days withdrawal time, and remained significant also 15 days after the last dose. An acute dose of Lu 19-005 did not modify the effects of d-amphetamine. The results are discussed in relation to the effect of prolonged treatment with other antidepressant drugs.
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On leave from Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, PL-31-343 Krakow, Poland.
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Nowak, G., Arnt, J., Hyttel, J. et al. Down-regulation of dopamine D-2, 5-HT2 receptors and β-adrenoceptors in rat brain after prolonged treatment with a new potential antidepressant, Lu 19-005. J. Neural Transmission 64, 227–238 (1985). https://doi.org/10.1007/BF01256469
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DOI: https://doi.org/10.1007/BF01256469