The effects of GABAB ligands on alcohol withdrawal in mice.
Recent research suggests that the GABAB receptor may mediate some of the acute effects of alcohol, but little is known of its involvement in alcohol withdrawal. Mice made dependent on alcohol exhibited tremor and tail arch when consumption ceased. Diazepam dose-dependently attenuated both tremor and tail arch, whereas baclofen had no effect on either of these two withdrawal symptoms. However, baclofen dose-dependently induced convulsant behaviour in the withdrawing mice, and this was significantly attenuated by the GABAB antagonists phaclofen (50 mg/kg) and CGP 35348 (300 mg/kg), but not BPBA (50 mg/kg). Phaclofen, BPBA, and CGP 35348, when administered alone and in combination with a single dose of baclofen, did have an effect on tremor, although the magnitude was small in comparison to that seen with diazepam. It appears that the GABAB receptor may play a role in mediating convulsions during alcohol withdrawal, and that in this system baclofen is proconvulsant.
Humeniuk
R E
RE
Department of Clinical and Experimental Pharmacology, University of Adelaide, South Australia.
White
J M
JM
Ong
J
J
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003975:Diazepam / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists; D051379:Mice; D008810:Mice, Inbred C57BL; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D018080:Receptors, GABA-B / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000523:psychology*; D014202:Tremor / Q000139:chemically induced
D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; C052329:phaclofen; C064718:3-amino-3-phenylpropionic acid; D000431:Ethanol; D010649:Phenylalanine; C066430:CGP 35348; D001418:Baclofen; D003975:Diazepam