Prevention of ethanol-induced behavioral stimulation by D-penicillamine: a sequestration agent for acetaldehyde.
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.
Font
Laura
L
Area de Psicobiología, Universitat Jaume I, Castelló, Spain.
Miquel
Marta
M
Aragon
Carlos M G
CM
D000079:Acetaldehyde / Q000037:antagonists & inhibitors / Q000097:blood*; D000818:Animals; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008124:Locomotion / Q000187:drug effects*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010396:Penicillamine / Q000494:pharmacology*
D000431:Ethanol; D010396:Penicillamine; D000079:Acetaldehyde