DECREASE OF CAMP AND INCREASE OF AMINO-AC IDS CONTENTS IN MOUSE-BRAINAFTER DIHYDROETORPHINE TOLERANCE

AIM: To study the mechanism of dihydroetorphine (DHE) tolerance, METHO DS: DHE tolerance was produced by repeated sc injections in progressiv ely increased doses to mice for 8 d. The concentrations of amino acids and cAMP were detected by RP-HPLC/fluorescence assay and radioimmunoa ssay, respectively. RESULTS: The basal contents of glutamic acid (Glu) , aspartic acid (Asp), and GABA in whole brain (cerebellum removed) we re increased respectively from 14.1 +/- 2.1, 3.0 +/- 0.4, and 1.8 +/- 0.8 mu mol/g tissue in control mice to 17.2 +/- 2.2, 4.1 +/- 0.6, and 3.2 +/- 1.0 mu mol/g tissue intolerant mice, and the rates of increase were 22.0 % (P < 0.05), 36.7 % (P < 0.01), and 77.8 % (P < 0.05 vs co ntrol), respectively, There was no significant difference in the basal contents of Gl(n) (5.1 +/- 1.0 vs 4.5 +/- 1.7 mu mol/g tissue of cont rol), The basal contents of cAMP in hypothalamus and, striatum were de creased respectively from 271 +/- 38 and 189 +/- 31 nmol/g tissue in c ontrol mice to 96 +/- 15 and 65 +/- 21 nmol/g tissue in tolerant mice (P < 0.01), and the rates of decrease were 64.6 % and 65.6 %, respecti vely, There was no significant difference of cAMP in cerebral cortex ( 72 +/- 20 vs 55 +/- 15 nmol/g tissue of control). CONCLUSION: The incr eases of Glu, Asp, and GABA in brain and the decrease of cAMP in hypot halamus and striatum were involved in DHE tolerance.