THE ONTOGENY OF CANNABINOID RECEPTORS IN THE BRAIN OF POSTNATAL AND AGING RATS

THE ONTOGENY OF CANNABINOID RECEPTORS IN THE BRAIN OF POSTNATAL AND AGING RATS
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DOI:
10.1016/0892-0362(94)00053-g
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发表时间:
1995-01-01
影响因子:
2.9
通讯作者:
HUTCHINGS, DE
HUTCHINGS, DE
中科院分区:
医学3区
文献类型:
--
作者:
BELUE, RC;HOWLETT, AC;HUTCHINGS, DE

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人们认识到,δ(9)-四氢大麻酚(THC)的许多生物学效应可以归因于在大脑中大量发现的大麻素受体。由于观察到大麻素药物具有一定的发育毒性,因此有必要检查新生大鼠大脑中大麻素受体的发育模式,然后进一步检查3至32个月大的大鼠大脑中衰老过程中的大麻素受体。使用放射性配体结合试验,这项研究表明,大麻素受体结合能力逐渐增加,从出生到出生后第60天(PND)。在纹状体内,结合的显著增加发生在PND 14和21之间。在小脑中,大麻素受体结合能力在出生后7天的时间内增加一倍,直到成年。皮质中的大麻素受体结合在PND 7和14之间加倍。在海马内,有小的增量增加,直到在PND 21达到最终的成人水平。在发育过程中,CP-55940的亲和力无显著变化。这些发现可能反映了神经元向具有大麻素受体的细胞的分化增加,或者在经历发育变化的区域中细胞体或投射上大麻素受体数量的增加。一旦达到成人大麻素受体水平,在正常衰老过程中,整个大脑制剂中的结合活性既不增加也不下降。
It is recognized that a number of the biological effects of Delta(9)-tetrahydrocannabinol (THC) can be attributed to a cannabinoid receptor found in abundance in the brain. Due to observations that cannabinoid drugs exert some developmental toxicity, it was of interest to examine the developmental pattern of cannabinoid receptors in the brain of neonatal rats through young adulthood, and then to further examine the cannabinoid receptor during the aging process in the brain of rats 3 to 32 months of age. Using radioligand binding assays, this study demonstrated that cannabinoid receptor binding capacity increases progressively from birth to postnatal day (PND) 60. Within the striatum, a significant increase in binding occurred between PNDs 14 and 21. In the cerebellum, cannabinoid receptor binding capacity doubled at 7-day postnatal intervals until adulthood. Cannabinoid receptor binding in the cortex doubled between PNDs 7 and 14. Within the hippocampus, there were small incremental increases until the final adult level was reached at PND 21. There was no significant alteration in the affinity for CP-55940 during development. These findings might reflect an increased differentiation of neurons into cells possessing cannabinoid receptors, or an increase in the number of cannabinoid receptors on cell bodies or projections in regions undergoing developmental changes. Once the adult cannabinoid receptor levels have been reached, binding activity in the whole brain preparation neither increased nor declined during the normal aging process.