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Prevention of Ethanol‐Induced Behavioral Stimulation by d‐Penicillamine: A Sequestration Agent for Acetaldehyde
Author(s) -
Font Laura,
Miquel Marta,
Aragon Carlos M. G.
Publication year - 2005
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 - 10.1097/01.alc.0000171945.30494.af
Subject(s) - penicillamine , acetaldehyde , ethanol , chemistry , pharmacology , saline , in vivo , caffeine , toxicity , stimulation , biochemistry , endocrinology , medicine , biology , organic chemistry , microbiology and biotechnology
Background: d‐Penicillamine, a sulfhydryl amino acid derived from penicillin, is a highly selective agent for sequestering in vivo acetaldehyde, the first metabolic product of ethanol. A substantial amount of research supports the idea that brain acetaldehyde, produced by central ethanol metabolism, plays a key role in determining some of the behavioral effects of ethanol administration. This study addressed two questions. First, we tested if d‐penicillamine was able to modify the depressant effects of acetaldehyde on behavior. Second, we studied the effect of d‐penicillamine on ethanol‐induced behavioral stimulation. Methods: Mice were pretreated with 75.00 mg/kg of d‐penicillamine, and 30 min later, they received acetaldehyde at 0, 100, 200, or 300 mg/kg intraperitoneally. Different groups of animals were treated with 0.0, 37.5, 75, 150, or 300 mg/kg of d‐penicillamine simultaneously 30, 90, 150, or 210 min before the intraperitoneal administration of saline or 1.2, 1.8, 2.4, 3.0, or 3.6 g/kg of ethanol, respectively. The specificity of d‐penicillamine effects was addressed using two drugs: cocaine (4 mg/kg) and caffeine (15 mg/kg). Results: Our results revealed that behavioral depression caused by acetaldehyde (200 and 300 mg/kg) could be attenuated by d‐penicillamine treatment. In addition, d‐penicillamine was also effective in lowering behavioral locomotion induced by ethanol (1.8 and 2.4 g/kg), without altering spontaneous locomotor activity. This sulfhydryl amino acid specifically modified the effect of ethanol on locomotion because cocaine‐ or caffeine‐induced locomotion was unaffected. In addition, blood ethanol levels were not different between d‐penicillamine‐ and saline‐pretreated mice. Conclusions: Behavioral effects produced by acetaldehyde and ethanol are blocked when animals are treated with d‐penicillamine, an effective sequestration agent for acetaldehyde. These results suggest that some of the psychopharmacological effects, classically attributed to ethanol, could be mediated by its first metabolite, acetaldehyde.