Peripheral, but not local or intracerebroventricular, administration of benzodiazepines attenuates evoked activity of locus coeruleus neurons.

To determine whether benzodiazepine receptors in the locus coeruleus (LC) regulate the firing of LC neurons, the effects of systemic, intracerebroventricular, and local administration of various benzodiazepines on LC activity were compared. Systemic administration of diazepam, chlordiazepoxide, and alprazolam in anesthetized rats markedly attenuated sensory-evoked activity of LC neurons while also suppressing, but to a lesser degree, spontaneous LC firing rates. When microinfused into the LC region, diazepam, chlordiazepoxide, and alprazolam reduced spontaneous LC firing rates to the same extent observed following systemic administration; however, unlike systemic administration, infusion of benzodiazepines into the LC failed to attenuate evoked LC activity. Similarly, intracerebroventricular administration of diazepam and chlordiazepoxide suppressed spontaneous, but not evoked, LC activity. These findings indicate that benzodiazepines suppress spontaneous LC firing by stimulating benzodiazepine receptors in the LC while attenuating evoked LC activity by stimulating benzodiazepine receptors that are neither in the LC nor accessible to benzodiazepines introduced into the ventricular system.