Differential effects of GABAA and GABAB agonists on sensitization to the locomotor stimulant effects of ethanol in DBA/2 J mice |
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Authors: | Julie Broadbent Wendy E Harless |
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Institution: | (1) Portland Alcohol Research Center, Oregon Health Sciences University, Portland, OR 97201-3098, USA, US;(2) Behavioral Neuroscience, L470, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA, US |
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Abstract: | Contemporary theories of drug abuse suggest that behavioral sensitization plays an important role in addiction. However,
few studies have examined the mechanisms underlying behavioral sensitization to ethanol. The present study examined the ability
of THIP (2, 4, or 8 mg/kg) and baclofen (5.0, 6.25, or 7.5 mg/kg), GABAA and GABAB agonists, respectively, to prevent development of sensitization to the locomotor stimulant effects of ethanol (2 g/kg) in
DBA/2 J mice. Ethanol was administered immediately before four 5-min activity trials conducted at 48-h intervals. Administration
of ethanol on each of the four trials resulted in behavioral sensitization in control groups. While having few effects on
activity when given alone, both GABA agonists completely blocked the acute stimulant response to ethanol on the first trial.
Administration of THIP prior to ethanol on each trial failed to prevent development of sensitization. In contrast, all doses
of baclofen blocked sensitization. Assessment of blood ethanol levels 15, 50 and 100 min after administration of ethanol indicated
that baclofen did not change the pharmacokinetics of ethanol. These results indicate an important role for GABAB receptors, but not GABAA receptors, in development of sensitization to the locomotor stimulant effects of ethanol.
Received: 11 April 1998 / Final version: 24 June 1998 |
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Keywords: | GABA agonists THIP Baclofen Sensitization Ethanol Locomotor activity DBA/2 J mice |
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