Dopamine receptor turnover rates in rat striatum are age-dependent

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-life-mature 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 reappearance of [3H]spiperone-binding sites. Other experiments indicate that chronic reserpine treatment, which produces dopamine receptor up regulation, also produces accelerated receptor recovery after EEDQ blockade. An age-related decline in dopamine receptor turnover, if present in humans and progressive into senescence, could be responsible for the increased risk of developing Parkinson disease and drug-induced parkinsonian-like extrapyramidal side effects with age. On the other hand, the more rapid receptor turnover rates seen in young rats may be a biochemical feature related to plasticity in the striatum during development.