EFFECTS OF LONG-TERM EXPOSURE TO DELTA(9)-THC ON EXPRESSION OF CANNABINOID RECEPTOR (CB1) MESSENGER-RNA IN DIFFERENT RAT-BRAIN REGIONS

The time course of changes across 21 days of continuous exposure to De lta(9)-tetrahydrocannabinol (Delta(9)-THC) was assessed for the level of cannabinoid receptor (CB1) mRNA expression in three different rat b rain regions: cerebellum, hippocampus and corpus striatum. Expression levels of CB1 mRNA were determined using semi-quantitative reverse tra nscriptase-polymerase chain reaction (RT-PCR) following a protocol whi ch included a gene standard, 28S ribonucleic acid protein (rRNA), for normalization of levels of RNA in the three different brain regions. T he levels of CB1 mRNA were assessed in four different rats at each of seven time points (6 h, and 1, 2, 3, 7, 14 and 21 days) during a 21-da y Delta(9)-THC one dose day(-1) (10 mg kg(-1)) treatment regimen. In t he cerebellum and hippocampus, CBI mRNA levels were increased above ve hicle control animals at 7 and 14 days of treatment. In the striatum t he levels of CB1 transcripts were severely reduced from days 2-14. CB1 message expression in all three brain areas returned to vehicle contr ol levels by day 21 of Delta(9)-THC treatment, a time at which behavio ral tolerance has been previously reported. An additional measure, rec eptor stimulated GTP gamma S binding, performed over the same time per iod revealed differential desensitization within the 3 brain areas as a function of chronic exposure to Delta(9)-THC. Hippocampus was the ea rliest to desensitize decreasing to 35% of control by treatment day 7, followed by a decrease in the cerebellum to that same level on day 14 of treatment. The striatum showed only half that degree of desensitiz ation (65%) over the entire 21-day treatment period. Comparisons sugge sts that CB1 message may be regulated by different effector systems in each of the three areas during chronic Delta(9)-THC exposure. (C) 199 8 ElIsevier Science B.V. All rights reserved.