CHRONIC ADMINISTRATION OF CANNABINOIDS REGULATES PROENKEPHALIN MESSENGER-RNA LEVELS IN SELECTED REGIONS OF THE RAT-BRAIN

This study was designed to examine the interactions between the cannab inoid and enkephalinergic systems in the rat brain. To this aim, we ha ve examined the effects of subchronic (5 days) administration (10 mg.k g(-1).day(-1); i.p.) of Delta(9)-tetrahydrocannabinol (THC) or R-metha nandamide (AM356) and chronic (18 days) administration with the synthe tic cannabinoid receptor agonist CP-55,940 (1 mg.kg(-1).day(-1); i.p.) on proenkephalin (PENK) mRNA levels in several brain regions of the r at. Twenty micrometer brain sections from striatum, nucleus accumbens, paraventricular nucleus, ventromedial nucleus, periaqueductal grey ma tter and mammillary nucleus were hybridized with an oligonucleotide pr obe complementary to PENK using in situ hybridization technique. Subch ronic administration of THC or AM356 increased PENK mRNA levels in the ventromedial nucleus of the hypothalamus, (82%) and (39%), in the per iaqueductal grey matter, (97%) and (49%), and mammillary nucleus, (43% ) and (9%), respectively. In contrast, both drugs were without effect in the striatum and nucleus accumbens. On the other hand, chronic admi nistration of CP-55,940 increased PENK mRNA levels in the striatum (44 %), nucleus accumbens (25%), paraventricular (31%) and ventromedial nu clei of the hypothalamus (41%). These results revealed that chronic ca nnabinoid administration increases opioid gene expression in the rat c entral nervous system and suggest an interaction between the cannabino id and enkephalinergic systems that may be part of a molecular integra tive response to behavioral and neurochemical alterations that occur i n cannabinoid drug abuse. (C) 1998 Elsevier Science B.V.