The ontogeny of cannabinoid receptors in the brain of postnatal and aging rats.
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.
Belue
R C
RC
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, MO 63104.
Howlett
A C
AC
Westlake
T M
TM
Hutchings
D E
DE
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001921:Brain / Q000254:growth & development*; D001923:Brain Chemistry / Q000502:physiology*; D002186:Cannabinoids / Q000494:pharmacology*; D003511:Cyclohexanols / Q000493:pharmacokinetics; D005260:Female; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000502:physiology*; D012727:Sex Characteristics; D013045:Species Specificity
D002186:Cannabinoids; D003511:Cyclohexanols; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol