Decrease of cAMP and increase of amino acids contents in mouse brain after dihydroetorphine tolerance
Abstract
AIM: To study the mechanism of dihydroetorphine (DHE) tolerance.
METHODS: DHE tolerance was produced by repeated s.c. injections in progressively increased doses to mice for 8 d. The concentrations of amino acids and cAMP were detected by RP-HPLC/fluorescence assay and radioimmunoassay, respectively.
RESULTS: The basal contents of glutamic acid (Glu), aspartic acid (Asp), and GABA in whole brain (cerebellum removed) were increased respectively from 14.1 +/- 2.1, 3.0 +/- 0.4, and 1.8 +/- 0.8 mumol/g tissue in control mice to 17.2 +/- 2.2, 4.1 +/- 0.6, and 3.2 +/- 1.0 mumol/g tissue in tolerant mice, and the rates of increase were 22.0% (P < 0.05), 36.7% (P < 0.01), and 77.8% (P < 0.05 vs control), respectively. There was no significant difference in the basal contents of Gln (5.1 +/- 1.0 vs 4.5 +/- 1.7 mumol/g tissue of control). The basal contents of cAMP in hypothalamus and striatum were decreased respectively from 271 +/- 38 and 189 +/- 31 nmol/g tissue in control 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%, respectively. There was no significant difference of cAMP in cerebral cortex (72 +/- 20 vs 55 +/- 15 nmol/g tissue of control).
CONCLUSION: The increases of Glu, Asp, and GABA in brain and the decrease of cAMP in hypothalamus and striatum were involved in DHE tolerance.
Keywords:
METHODS: DHE tolerance was produced by repeated s.c. injections in progressively increased doses to mice for 8 d. The concentrations of amino acids and cAMP were detected by RP-HPLC/fluorescence assay and radioimmunoassay, respectively.
RESULTS: The basal contents of glutamic acid (Glu), aspartic acid (Asp), and GABA in whole brain (cerebellum removed) were increased respectively from 14.1 +/- 2.1, 3.0 +/- 0.4, and 1.8 +/- 0.8 mumol/g tissue in control mice to 17.2 +/- 2.2, 4.1 +/- 0.6, and 3.2 +/- 1.0 mumol/g tissue in tolerant mice, and the rates of increase were 22.0% (P < 0.05), 36.7% (P < 0.01), and 77.8% (P < 0.05 vs control), respectively. There was no significant difference in the basal contents of Gln (5.1 +/- 1.0 vs 4.5 +/- 1.7 mumol/g tissue of control). The basal contents of cAMP in hypothalamus and striatum were decreased respectively from 271 +/- 38 and 189 +/- 31 nmol/g tissue in control 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%, respectively. There was no significant difference of cAMP in cerebral cortex (72 +/- 20 vs 55 +/- 15 nmol/g tissue of control).
CONCLUSION: The increases of Glu, Asp, and GABA in brain and the decrease of cAMP in hypothalamus and striatum were involved in DHE tolerance.