Muscimol-associated changes in local cerebral glucose use following chronic diazepam administration.
Local cerebral glucose use (LCGU) was determined in parallel groups of conscious rats receiving muscimol (1.5 mg/kg i.v.) after either saline pretreatment (28 days i.p.), saline pretreatment (27 days i.p.) followed by a single dose of diazepam (5 mg/kg i.p.) 24 h prior to muscimol administration, or chronic diazepam pretreatment (5 mg/kg i.p. daily for 28 days). Acute administration of muscimol produced a significant reduction in LCGU in 25 out of 66 structures examined compared with vehicle-treated controls. The pattern of reductions was heterogeneous. Thalamic and most cortical areas showed reductions of the order of 30-45%, whereas more modest depressions of 15-20% were observed in some limbic structures (e.g. basolateral amygdala, anterior thalamic nuclei, nucleus accumbens, subiculum). This contrasts with the more extensive and homogeneous pattern of LGCU reductions (around 20%) produced by diazepam. Neither acute diazepam treatment the previous day nor chronic diazepam pretreatment altered the LGCU response to muscimol. These data suggest that high-affinity GABA receptor-mediated responses are unchanged by both acute and chronic benzodiazepine pretreatment. It would appear unlikely that alterations in these responses contribute to the mechanism of benzodiazepine tolerance.
Brett
R R
RR
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, U.K.
Pratt
J A
JA
D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D003847:Deoxyglucose / Q000097:blood / Q000378:metabolism; D003864:Depression, Chemical; D003975:Diazepam / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D008297:Male; D009118:Muscimol / Q000494:pharmacology*; D051381:Rats
D001786:Blood Glucose; D009118:Muscimol; D003847:Deoxyglucose; D005947:Glucose; D003975:Diazepam