GABAA-benzodiazepine receptors in the striatum are involved in the sedation produced by a moderate, but not an intoxicating ethanol dose in outbred Wistar rats.
The role of the dorsal striatum in mediating the sedation produced by a moderate (0.75 g/kg) and an intoxicating (1.25 g/kg) EtOH dose was investigated in the open field by determining the capacity of direct intrastriatal injections of RY 008, a partial inverse agonist of the benzodiazepine (BDZ) receptor, to antagonize EtOH's effects. SR 95531, the competitive high-affinity GABAA antagonist was used as a reference compound. Intrastriatal RY 008 (50, 500 ng) and SR 95531 (50 ng) antagonized the sedation produced by the 0.75 g/kg EtOH dose. However, RY 008 did not alter the sedation produced by the 1.25 g/kg dose. RY 008 alone was without effect. RY 008 also failed to negatively modulate GABAergic function at alpha1beta2gamma2 or alpha6beta2gamma2 receptor subtypes expressed in Xenopus oocytes. Intrastriatal modulation of the moderate EtOH dose was site specific: no antagonism by RY 008 after intraaccumbens infusions was observed. The results suggest that central GABAA-BDZ receptors in the dorsal striatum play an important role in mediating the sedation produced by a moderate EtOH dose in the open field.
June
H L
HL
Department of Psychology, Purdue School of Science, Indiana University-Purdue University, Indianapolis, IN 46202, USA. hjune@iupui.edu
Cason
C R
CR
Cheatham
G
G
Lui
R
R
Gan
T
T
Cook
J M
JM
D000435:Alcoholic Intoxication / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D001386:Azides / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*; D014981:Xenopus / Q000378:metabolism
D001386:Azides; D018682:GABA Agents; D058785:GABA-A Receptor Agonists; D006993:Hypnotics and Sedatives; D011724:Pyridazines; C113975:RY 008; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D000431:Ethanol; D005442:Flumazenil; C042957:Ro 15-4513; C049853:gabazine