[Decrease of cAMP and increase of amino acids contents in mouse brain after dihydroetorphine tolerance].
OBJECTIVE
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).


CONCLUSIONS
The increases of Glu, Asp, and GABA in brain and the decrease of cAMP in hypothalamus and striatum were involved in DHE tolerance.
Chen
M H
MH
Department of Neurobiology, School of Basic Medical Sciences, Shanghai Medical University, China. smulib@public.sta.net.cn
Li
Q S
QS
Shen
Y
Y
Ma
H J
HJ
Zuo
X J
XJ
D000596:Amino Acids / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D004361:Drug Tolerance; D005048:Etorphine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D051379:Mice; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000596:Amino Acids; D000701:Analgesics, Opioid; D001224:Aspartic Acid; D018698:Glutamic Acid; D005048:Etorphine; D005680:gamma-Aminobutyric Acid; D000242:Cyclic AMP; C034765:18,19-dihydroetorphine