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Tolerance to Adenosine's Accentuation of Ethanol‐Induced Motor Incoordination in Ethanol‐Tolerant Mice
Author(s) -
Dar M. Saeed,
Clark Mike
Publication year - 1992
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1992.tb00710.x
Subject(s) - adenosine , ethanol , adenosine receptor , chemistry , medicine , endocrinology , receptor , desensitization (medicine) , pharmacology , biochemistry , agonist
Our previously published reports have provided data that have supported a functional correlation between ethanol‐induced changes in the characteristics of adenosine receptor, adenosine uptake and release in the brain, and ethanol‐induced motor incoordination. The present data demonstrated a cross‐tolerance between ethanol and adenosine further supporting the hypothesis that brain adenosine modulates the motor impairing effects of ethanol. Mice that received (‐)‐N 6 ‐cyclohexyladenosine (CHA) [0.25 mg/kg/day, intraperitoneal (ip)] for 10 days exhibited marked attenuation (cross‐tolerance) to acute ethanol‐induced motor incoordination compared with chronic saline (ip) controls. The attenuation of acute ethanol‐induced motor incoordination was essentially same in animals that received CHA (25 ng/5 μl/day for 10 days) by the intracerebroventricular (icv) route as opposed to the controls that chronically received artificial cerebral spinal fluid by the same route. Similarly, tolerance was exhibited to acute CHA (0.125 mg/kg ip and 12.5 ng/5 μl icv) by animals fed liquid ethanol (19.5 g/kg/24 hr) for 10 days compared with none in the pair‐fed sucrose controls. Scatchard plots using cerebellar tissue homogenates from animals given chronic CHA or chronic ethanol indicated no change in B max and/or K d values for CHA binding when compared with CHA binding in tissues from their respective controls. However, a lack of any change in the binding characteristics cannot rule out the involvement of adenosine receptors in the observed cross‐tolerance between ethanol and CHA. The results may suggest desensitization of adenosine A, receptors due to chronic CHA and ethanol as an alternate possible explanation in the development of cross‐tolerance between adenosine (CHA) and ethanol.