In rats, THC at 2 mg/kg caused a specific 33% reduction of PGE2 when measured in a bioassay procedure (Coupar and Taylor, 1982). This was accompanied by the induction of hypothermia and catatonia followed by sedation. Two points need to be made on these observations. First, is the non-specific nature of the measurements and second, is the possible involvement of THC metabolites in the inhibitory effect on PG levels. By contrast, in a study using radioimmunoassay, similar doses of THC in the rat produced 2-3 fold increases in brain levels of
PGE2 (Bhattacharya, 1986). Thus, as was the case with in vitro studies, the experimental conditions appear to play an important role in the direction of the THC effect on PG levels.
The above findings were supported in a report showing both increases and decreases in the amounts of THC-induced PG synthesis in various brain regions (Reichman et al, 1987). THC-induced brain levels of PGE2 in the rat could be reduced by the prior administration of i.v. antiserum to PGE2 (Hunter et al., 1991). This finding suggests the possibility that the brain PGs may be of peripheral origin since it can be expected that the antiserum would not cross the blood-brain barrier.
One study on PG-CB interactions in humans has been published (Perez-Reyes et al., 1991). Blood levels of PGs when measured by immunoassay were seen to increase about twofold shortly after volunteers smoked a standardized marijuana cigarette. Both the increase in PG concentration and several of the effects of the drug were reduced by the prior administration of indomethacin, a potent inhibitor of eicosanoid synthesis. In particular, the THC-induced impairment of time estimation was reduced greatly by indomethacin.
Similar effects were observed with eicosanoid inhibitors in the THC-induced cataleptic response in mice, suggesting that this action may involve mediation by prostaglandins (Fairbairn and Pickens, 1979; Burstein et al., 1987). In addition, the cataleptic effect was restored by the administration of PGE2. Further evidence for the role of eicosanoids is found in the observation that mice fed a diet deficient in arachidonic acid exhibited a reduced cataleptic response to THC whereas exogenous arachidonic acid restored catalepsy (Fairbairn and Pickens, 1980). Finally, additional support for the involvement of PGs in THC-induced catalepsy is provided by the report that anti-PGE2 antibodies suppress THC-induced responses in mice (Burstein etal., 1989).
Further evidence suggesting that prostaglandins have a role in the behavioral effects of THC were recently reported by Yamaguchi et al. (2001). Using the rat lever-pressing performance model, they found that the effects of both THC and HU-210 were reduced by several diverse COX inhibitors. Moreover, the cannabinoid response was mimicked by the i.c.v. administration of PGE2. It is further pointed out that both the CBX and PGE receptors are highly expressed in the sub-stantia nigra region in the brain.
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