Chronic treatment with CP-55,940 regulates corticotropin releasing factor and proopiomelanocortin gene expression in the hypothalamus and pituitary gland of the rat

The purpose of the present study was to explore the molecular mechanisms by which the cannabinoid system may interact with the hypothalamic-pituitary adrenal axis and the proopiomelanocortin opioid system. To this aim and by using in situ hybridization histochemistry, the effects of chronic (18 days ) administration with the synthetic cannabinoid receptor agonist {(-)-cis-3 -[2-hydroxy-4-(1,1,-dimethylheptyl)-phenyl]-trans-4(-3-hydroxypropyl)cycloh exanol)}, CP-55,940 (1 mg/kg/day; i.p.) on corticotropin releasing factor a nd proopiomelanocortin gene expression were examined in the paraventricular and arcuate nuclei of the hypothalamus and anterior and intermediate lobes of the pituitary gland in the rat. Chronic administration with CP-55,940 i ncreased corticotropin releasing factor mRNA levels (41%) in the paraventri cular nucleus and proopiomelanocortin mRNA levels in the arcuate nucleus (2 5%) and anterior lobe of the pituitary (30%), but decreased (28%) of proopi omelanocortin transcript amounts in the intermediate lobe of the pituitary. These results revealed that chronic cannabinoid administration enhances co rticotropin releasing factor and proopiomelanocortin gene expression in the hypothalamus and anterior pituitary, a process that may be considered as p art of a molecular integrative response to the stress associated to cannabi noid drug abuse.