CHRONIC CP-55,940 ALTERS CANNABINOID RECEPTOR MESSENGER-RNA IN THE RAT-BRAIN - AN IN-SITU HYBRIDIZATION STUDY

USING in situ hybridization we found that chronic treatment with CP-55 ,940 (0.4 mg kg(-1), i.p. daily for 11 days), a synthetic cannabinoid receptor ligand, changed cannabinoid receptor mRNA levels in rat brain . CP-55,940 produced the expected tolerance: the decrease in locomotor activity (75%) caused by an acute dose was diminished to 25% after th e 11 days of treatment. Thirty minutes after the last injection the an imals were killed and in situ hybridization indicated that the levels of cannabinoid receptor mRNA in the caudate-putamen were reduced by 33 %, with no alteration in the other brain areas. We suggest that the al tered cannabinoid receptor expression is part of the adaptive changes underlying cannabinoid tolerance.