1984
DOI: 10.1073/pnas.81.12.3910
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Dopamine receptor turnover rates in rat striatum are age-dependent.

Abstract: The time course of recovery of [3H~spiperone binding in the rat striatum after a single injection of the irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) shows that a slower rate of regeneration/turnover of D-2 dopamine receptors occurs in mid-lifemature versus young male rats. This slower receptor recovery reflects relatively slower rates of both receptor synthesis and degradation. Studies using cycloheximide indicate that protein synthesis plays a significant role in the reappear… Show more

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Cited by 62 publications
(29 citation statements)
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“…Although not examined in the present study, repeated reserpine treatment does cause D 2 -like receptor upregulation in adult rats (Burt et al 1977;Leff et al 1984); therefore, the present data are consistent with either a "conformational change" or "receptor reserve" explanation of partial agonist functioning.…”
Section: Discussionsupporting
confidence: 88%
“…Although not examined in the present study, repeated reserpine treatment does cause D 2 -like receptor upregulation in adult rats (Burt et al 1977;Leff et al 1984); therefore, the present data are consistent with either a "conformational change" or "receptor reserve" explanation of partial agonist functioning.…”
Section: Discussionsupporting
confidence: 88%
“…The above predictions are in accordance with the observation that dopamine turnover is not increased in the brains of schizophrenics and is possibly decreased (Leff et al, 1984) Furthermore, if there are too few dapamine D2 receptors, the combined effects of neuroleptic blockade and receptor upregulation are unlikely to result in an effective D2 dopamine occupancy in the normal range. The idea that schizophrenia may be accompanied by too few or too many D2 receptors is in the spirit of the recently described picture where too much or too little D l activation can result in impaired cognitive performance (Desimone, 1995).…”
Section: Discussionsupporting
confidence: 74%
“…If B,cax is the average dopamine D2 receptor density for normals, then the average occupancy, or concentration of receptor-dopamine complexes is To take into account the changes in dopamine receptor density due to degradation and synthesis, we use a model previously used for acetylcholine receptors (Fambrough et al, 1977) and dopamine receptors by Leff et al (1984). Letting R(t) now standfor the density of receptors at time t, this quantity is given by the solution of the differential equation where a is the degradation rate and P i s rate of synthesis, assumed constant.…”
Section: Methodsmentioning
confidence: 99%
See 1 more Smart Citation
“…Times for 50% recovery of binding sites were between 35 and 50 h and these were approximately doubled in the presence of cycloheximide. These times are in good accord with those determined for a number of plasmalemmal receptors including a, -adrenoceptors (23-33 h; Sladeczek and Bockaert 1982;Mauger et al 1982 tion rates of 0.02-0.03 h-' and production rates of 1.7-3.2 fmol-mg protein-' -h-I have been reported for a -adrenoceptors and dopamine receptors (Mauger et al 1982;Sladeczek and Bockaert 1982;Leff et al 1984) which also concur with those obtained for nitrendipine binding sites (Table 2). Administration of cycloheximide reduced approximately equally the rates of binding site appearance and degradation.…”
Section: Fig 5 (A) Dose-response Curves To C a 2 + In K+-depolarizesupporting
confidence: 74%