Muscimol-associated changes in local cerebral glucose use following chronic diazepam administration

Abstract

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.