Repeated administration of Δ9-tetrahydrocannabinol produces a differential time related responsiveness on proenkephalin, proopiomelanocortin and corticotropin releasing factor gene expression in the hypothalamus and pituitary gland of the rat

The purpose of the present study was to explore the time related effects of repeated administration of Delta(9)-tetrahydrocannabinol on opioid and corticotropin releasing factor gene expression in the hypothalamus and pituitary gland of the rat. By using in situ hybridization histochemistry, the effects of Delta(9)-tetrahydrocannabinol (THC, 5 mg/kg per day; i.p.) were examined after 1, 3, 7 and 14 days of repeated administration on; (1) proenkephalin gene expression in the paraventricular (PVN) and ventromedial nuclei (VMN) of the hypothalamus, (2) proopiomelanocortin gene expression in the arcuate nucleus (ARC) of the hypothalamus and anterior (AL) and intermediate lobe (IL) of the pituitary gland, and (3) corticotropin releasing factor gene expression in the PVN. The results revealed that, in most of the hypothalamic and pituitary regions examined, repeated cannabinoid administration upregulates opioid and corticotropin releasing factor gene expression. However, the onset, the degree of magnitude of gene expression reached and the time related effects produced by repeated administration with Delta(9)-tetrahydrocannabinol are dependent upon the brain and pituitary regions examined. Taken together, the results of the present study suggest that cannabinoids produce a time related differential responsiveness in opioid and corticotropin releasing factor gene expression, in areas of the hypothalamus and pituitary that may be related, at least in part, to a molecular integrative response to behavioral, endocrine and neurochemical alterations that occur in cannabinoid drug abuse. (C) 1999 Elsevier Science Ltd. All rights reserved.